Curation
Showing variants that contain the term
Below are conditions that were reviewed by an expert panel and/or are in the Genetic Testing Registry (GTR) according to ClinVar. The data presented does not diagnose disease and has no guarantees of reporting accuracy. We report heterozygous variants as yellow and homozygous variants as red. A red or yellow variant does not necessarily mean one has or carries a condition or disease. This is for research and educational purposes only.
Gene:
LCT;MCM6
Variant:
c.-13907C>T
rsID: rs4988235
Ref Allele: G
Alt Allele: A
Freq: 16.1342%
CADD: 13.46
ClinVar Submissions (1)
Last Evaluated: Nov 20, 2018
Review Status: no assertion criteria provided
Number of Submitters: 1
Clinical Significance: association
Assembly: GRCh37
Chromosome/Position: 2:136608646
OMIM Allelic Variant: 601806.0001
Expert Reviewed
Hetero
Gene:
AMPD1
Variant:
c.133C>T
(p.Gln45Ter)
rsID: rs17602729
Ref Allele: G
Alt Allele: A
Freq: 3.8139%uncommon
CADD: 36
ClinVar Submissions (6)
Myoadenylate deaminase deficiency (MMDD) is an autosomal recessive condition that can manifest as exercise-induced muscle pain, occasionally associated with rhabdomyolysis and/or increased serum creatine kinase, or even infantile hypotonia. However, the finding of homozygous mutations among asymptomatic individuals have suggested to some (e.g., Verzijl et al., 1998) that AMPD1 deficiency may be a harmless entity (summary by Castro-Gago et al., 2011). Genetta et al. (2001) stated that AMPD1 deficiency is the most prevalent genetic disease in humans, the number of people heterozygous approaching 10% of Caucasians and individuals of African descent (Sabina et al., 1989). A small percentage of homozygous-deficient individuals, approximately 1.8% of the population, display symptoms of chronic fatigue and lost productivity as well as a predisposition to stress-related ailments, including heart disease and stroke, according to Genetta et al. (2001).
Last Evaluated: Jun 27, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 6
Clinical Significance: Conflicting interpretations of pathogenicity, other
Assembly: GRCh37
Chromosome/Position: 1:115236057
OMIM Allelic Variant: 102770.0001
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Jun 27, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 6
Clinical Significance: Conflicting interpretations of pathogenicity, other
Assembly: GRCh37
Chromosome/Position: 1:115236057
OMIM Allelic Variant: 102770.0001
The individual has two copies of the variant, which suggests they may manifest the associated condition or trait. This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Low clinical importance, Likely pathogenic — Causes Adenosine Deaminase Deficiency in a recessive manner. Most of the time individuals do not report symptoms, but when symptoms do exist they to be post-exercise symptoms of muscle weakness, muscle pain, and getting tired more quickly.
Expert Reviewed Clinically Significant Conflicting/Uncertain
Homo
Below are drug responses that were reviewed by an expert panel according to ClinVar. The data presented has no guarantees of reporting accuracy. Heterozygous variants are reported as yellow and homozygous variants as red. Reference alleles may be modified to match risk. While a red or yellow variant could indicate a suboptimal response to drug, it doesn't necessarily mean one won't respond well to it. This is for research and educational purposes only.
Gene:
GSTP1
Variant:
c.313A>G
(p.Ile105Val)
rsID: rs1695
Ref Allele: A
Alt Allele: G
Freq: 35.2636%
CADD: 0.035
ClinVar Submissions (2)
A benign or malignant neoplasm that affects the colon or rectum. Representative examples of benign neoplasms include lipoma and leiomyoma. Representative examples of malignant neoplasms include carcinoma, lymphoma, and sarcoma. Colorectal adenomas always exhibit epithelial dysplasia and are considered premalignant neoplasms.
Last Evaluated: May 03, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:67352689
Last Evaluated: May 03, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:67352689
Last Evaluated: May 03, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:67352689
Last Evaluated: May 03, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:67352689
Last Evaluated: May 03, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:67352689
Insufficiently evaluated pharmacogenetic — Hematological toxicity with fluoruracil.
Expert Reviewed drug response
Hetero
Gene:
CYP19A1
Variant:
c.*161T>G
rsID: rs4646
Ref Allele: A
Alt Allele: C
Freq: 33.5663%
CADD: 0.416
ClinVar Submissions (2)
Last Evaluated: Feb 06, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 15:51502844
Last Evaluated: Feb 06, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 15:51502844
Last Evaluated: Feb 06, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 15:51502844
Last Evaluated: Feb 06, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 15:51502844
Last Evaluated: Feb 06, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 15:51502844
Last Evaluated: Feb 06, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 15:51502844
Last Evaluated: Feb 06, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 15:51502844
Last Evaluated: Feb 06, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 15:51502844
Last Evaluated: Feb 06, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 15:51502844
Last Evaluated: Feb 06, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 15:51502844
Last Evaluated: Feb 06, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 15:51502844
Insufficiently evaluated pharmacogenetic — associated with response to a drug letrozole in cancer patients
Expert Reviewed drug response
Homo
Gene:
COMT
Variant:
c.472G>A
(p.Val158Met)
rsID: rs4680
Ref Allele: G
Alt Allele: A
Freq: 36.9209%
CADD: 13.15
ClinVar Submissions (3)
Last Evaluated: Dec 20, 2017
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 22:19951271
OMIM Allelic Variant: 116790.0001
Last Evaluated: Dec 20, 2017
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 22:19951271
OMIM Allelic Variant: 116790.0001
Last Evaluated: Dec 20, 2017
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 22:19951271
OMIM Allelic Variant: 116790.0001
Insufficiently evaluated pathogenic — A codominant allele affecting COMT enzyme activity, considered a benign functional polymorphism. Some claims of association with schizophrenia, Possibly provides advantage in memory and attention tasks ("worrier strategy").
Expert Reviewed drug response
Hetero
Gene:
SOD2
Variant:
c.47T>C
(p.Val16Ala)
rsID: rs4880
Ref Allele: A
Alt Allele: G
Freq: 41.0743%
CADD: 13.03
ClinVar Submissions (2)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 6:160113872
OMIM Allelic Variant: 147460.0001
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 6:160113872
OMIM Allelic Variant: 147460.0001
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 6:160113872
OMIM Allelic Variant: 147460.0001
Expert Reviewed drug response
Hetero
Gene:
ADD1
Variant:
c.1378G>T
(p.Gly460Trp)
rsID: rs4961
Ref Allele: G
Alt Allele: T
Freq: 20.8466%
CADD: 31
ClinVar Submissions (2)
Last Evaluated: Oct 14, 2015
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 4:2906707
OMIM Allelic Variant: 102680.0001
Last Evaluated: Oct 14, 2015
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 4:2906707
OMIM Allelic Variant: 102680.0001
Insufficiently evaluated pathogenic — This variant is associated with salt-sensitivity in patients with hypertension.
Expert Reviewed drug response
Hetero
Gene:
GNB3
Variant:
c.825C>T
(p.Ser275=)
rsID: rs5443
Ref Allele: C
Alt Allele: T
Freq: 49.2212%
CADD: 1.008
ClinVar Submissions (1)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 12:6954875
Expert Reviewed drug response
Hetero
Gene:
F5
Variant:
c.1601G=
(p.Arg534=)
rsID: rs6025
Ref Allele: C
Freq: 0.599%rare
CADD: 18.92
ClinVar Submissions (2)
Last Evaluated: Nov 28, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:169519049
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Nov 28, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:169519049
The data does not specify whether the genetic variant is autosomal recessive or autosomal dominant. For a definitive determination, refer to resources such as OMIM.
Expert Reviewed Clinically Significant drug response
Normal
Gene:
GP1BA
Variant:
c.482C>T
(p.Thr161Met)
rsID: rs6065
Ref Allele: C
Alt Allele: T
Freq: 13.1589%
CADD: 2.263
ClinVar Submissions (2)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 17:4836381
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 17:4836381
Expert Reviewed drug response
Normal
Gene:
HTR1A
Variant:
c.-1019G>C
rsID: rs6295
Ref Allele: G
Alt Allele: C
Freq: 45.3275%
CADD: 1.898
ClinVar Submissions (2)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Mar 09, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 5:63258565
Last Evaluated: Mar 09, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 5:63258565
Expert Reviewed drug response
Hetero
Gene:
VKORC1
Variant:
c.*134G>A
rsID: rs7294
Ref Allele: C
Alt Allele: T
Freq: 41.9728%
CADD: 3.208
ClinVar Submissions (2)
Last Evaluated: Dec 11, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:31102321
Last Evaluated: Dec 11, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:31102321
Last Evaluated: Dec 11, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:31102321
Last Evaluated: Dec 11, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:31102321
Expert Reviewed drug response
Normal
Gene:
APOE
Variant:
c.526C>T
(p.Arg176Cys)
rsID: rs7412
Ref Allele: C
Alt Allele: T
Freq: 7.508%
CADD: 25.1
ClinVar Submissions (4)
Last Evaluated: Feb 21, 2017
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:45412079
OMIM Allelic Variant: 107741.0001
Last Evaluated: Feb 21, 2017
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:45412079
OMIM Allelic Variant: 107741.0001
Last Evaluated: Feb 21, 2017
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:45412079
OMIM Allelic Variant: 107741.0001
Last Evaluated: Feb 21, 2017
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:45412079
OMIM Allelic Variant: 107741.0001
Last Evaluated: Feb 21, 2017
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:45412079
OMIM Allelic Variant: 107741.0001
Last Evaluated: Feb 21, 2017
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:45412079
OMIM Allelic Variant: 107741.0001
The data does not specify whether the genetic variant is autosomal recessive or autosomal dominant. For a definitive determination, refer to resources such as OMIM.
Insufficiently evaluated pharmacogenetic — This is generally known as the ApoE2 variant of ApoE and is associated with a decreased risk of Alzheimer's disease.
Expert Reviewed Clinically Significant drug response
Normal
Gene:
ERCC1
Variant:
c.354T>C
(p.Asn118=)
rsID: rs11615
Ref Allele: A
Alt Allele: G
Freq: 33.107%
CADD: 9.79
ClinVar Submissions (2)
Last Evaluated: Dec 06, 2016
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:45923653
Xeroderma pigmentosum (XP) is characterized by: Sun sensitivity (severe sunburn with blistering, persistent erythema on minimal sun exposure in ~60% of affected individuals), with marked freckle-like pigmentation of the face before age two years in most affected individuals; Sunlight-induced ocular involvement (photophobia, keratitis, atrophy of the skin of the lids); Greatly increased risk of sunlight-induced cutaneous neoplasms (basal cell carcinoma, squamous cell carcinoma, melanoma). Approximately 25% of affected individuals have neurologic manifestations (acquired microcephaly, diminished or absent deep tendon stretch reflexes, progressive sensorineural hearing loss, and progressive cognitive impairment). The most common causes of death are skin cancer, neurologic degeneration, and internal cancer. The median age at death in persons with XP with neurodegeneration (29 years) was found to be younger than that in persons with XP without neurodegeneration (37 years).
Last Evaluated: Dec 06, 2016
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:45923653
Last Evaluated: Dec 06, 2016
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:45923653
Last Evaluated: Dec 06, 2016
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:45923653
Last Evaluated: Dec 06, 2016
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:45923653
Last Evaluated: Dec 06, 2016
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:45923653
Expert Reviewed drug response
Hetero
Gene:
XRCC1
Variant:
c.1196A>G
(p.Gln399Arg)
rsID: rs25487
Ref Allele: T
Alt Allele: C
Freq: 26.0383%
CADD: 17.47
ClinVar Submissions (1)
Last Evaluated: Dec 07, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:44055726
Last Evaluated: Dec 07, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:44055726
Last Evaluated: Dec 07, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:44055726
Last Evaluated: Dec 07, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:44055726
Last Evaluated: Dec 07, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:44055726
Expert Reviewed drug response
Homo
Gene:
TANC1
Variant:
c.61+13908C>A
rsID: rs264588
Ref Allele: C
Alt Allele: A
Freq: 17.512%
CADD: 2.418
ClinVar Submissions (1)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:159936391
Expert Reviewed drug response
Normal
Gene:
TANC1
Variant:
c.62-3284C>G
rsID: rs264631
Ref Allele: C
Alt Allele: G
Freq: 19.4089%
CADD: 0.854
ClinVar Submissions (1)
Last Evaluated: Feb 13, 2018
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:159950865
Expert Reviewed drug response
Normal
Gene:
TANC1
Variant:
c.61+6948A>G
rsID: rs264651
Ref Allele: A
Alt Allele: G
Freq: 10.7428%
CADD: 2.028
ClinVar Submissions (1)
Last Evaluated: Feb 13, 2018
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:159929431
Expert Reviewed drug response
Normal
Gene:
CALU
Variant:
c.582+133A>G
rsID: rs339097
Ref Allele: A
Alt Allele: G
Freq: 4.353%uncommon
CADD: 0.197
ClinVar Submissions (1)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:128399224
Expert Reviewed drug response
Normal
Gene:
MC4R
Variant:
g.60215554C>A
rsID: rs489693
Ref Allele: C
Alt Allele: A
Freq: 35.1238%
CADD: 0.325
ClinVar Submissions (1)
Last Evaluated: Jun 22, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 18:57882787
Last Evaluated: Jun 22, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 18:57882787
Clozapine is one of the most effective antipsychotics available in the treatment of schizophrenia and the only antipsychotic found to be effective in treatment-resistant schizophrenia. Clozapine is also used to reduce the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder. Compared to typical antipsychotics, clozapine is far less likely to cause movement disorders, known as extrapyramidal side effects, which include dystonia, akathisia, parkinsonism, and tardive dyskinesia. However, there are significant risks associated with clozapine therapy that limits its use to only the most severely ill patients who have not responded adequately to standard drug therapy. Most notably, because of the risk of clozapine-induced agranulocytosis, clozapine treatment requires monitoring of white blood counts and absolute neutrophil counts, and in the US, the FDA requires that patients receiving clozapine be enrolled in a computer-based registry. Clozapine is metabolized in the liver by the cytochrome P450 (CYP) system of enzymes. CYP1A2 is the main CYP isoform in clozapine metabolism and CYP1A2 activity is an important determinant of clozapine dose. Other CYP enzymes involved in clozapine metabolism include CYP2D6 and CYP3A4. Approximately 6-10% of Caucasians have reduced activity of CYP2D6 ("poor metabolizers"). These individuals may develop higher than expected plasma concentrations of clozapine with usual doses. The FDA-approved drug label for clozapine states that a dose reduction may be necessary in patients who are CYP2D6 poor metabolizers.
Last Evaluated: Jun 22, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 18:57882787
Last Evaluated: Jun 22, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 18:57882787
Last Evaluated: Jun 22, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 18:57882787
Last Evaluated: Jun 22, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 18:57882787
Last Evaluated: Jun 22, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 18:57882787
Last Evaluated: Jun 22, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 18:57882787
Last Evaluated: Jun 22, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 18:57882787
Expert Reviewed drug response
Normal
Gene:
CHRNA3
Variant:
c.1390-2867C>T
rsID: rs578776
Ref Allele: G
Alt Allele: A
Freq: 44.5288%
CADD: 1.384
ClinVar Submissions (1)
Last Evaluated: Apr 12, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 15:78888400
Expert Reviewed drug response
Normal
Gene:
APOA5
Variant:
c.-644C>T
rsID: rs662799
Ref Allele: G
Alt Allele: A
Freq: 16.2939%
CADD: 4.823
ClinVar Submissions (1)
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:116663707
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:116663707
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:116663707
Insufficiently evaluated pharmacogenetic — associated with the triglyceride levels and the risk of first heart attack
Expert Reviewed drug response
Homo
Gene:
DYNC2H1
Variant:
g.103547430A>G
rsID: rs716274
Ref Allele: A
Alt Allele: G
Freq: 43.7101%
CADD: 0.621
ClinVar Submissions (1)
Last Evaluated: Oct 14, 2015
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:103418158
Last Evaluated: Oct 14, 2015
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:103418158
Expert Reviewed drug response
Normal
Gene:
LTC4S
Variant:
c.-444A>C
rsID: rs730012
Ref Allele: A
Alt Allele: C
Freq: 17.0128%
CADD: 1.936
ClinVar Submissions (1)
Last Evaluated: Oct 28, 2015
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 5:179220638
Expert Reviewed drug response
Normal
Gene:
PNPLA3
Variant:
c.444C>G
(p.Ile148Met)
rsID: rs738409
Ref Allele: C
Alt Allele: G
Freq: 26.2181%
CADD: 15.7
ClinVar Submissions (2)
Last Evaluated: Nov 27, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 22:44324727
Last Evaluated: Nov 27, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 22:44324727
Last Evaluated: Nov 27, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 22:44324727
Last Evaluated: Nov 27, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 22:44324727
Last Evaluated: Nov 27, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 22:44324727
Last Evaluated: Nov 27, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 22:44324727
Expert Reviewed drug response
Hetero
Gene:
CCHCR1
Variant:
c.1581-597T>C
rsID: rs746647
Ref Allele: A
Alt Allele: G
Freq: 22.0447%
CADD: 5.575
ClinVar Submissions (1)
Last Evaluated: Jun 22, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 6:31114182
Expert Reviewed drug response
Normal
Gene:
CYP3A5
Variant:
c.219-237G>A
rsID: rs776746
Ref Allele: C
Alt Allele: T
Freq: 37.8594%
CADD: 3.863
ClinVar Submissions (1)
Last Evaluated: Mar 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:99270539
Last Evaluated: Mar 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:99270539
Last Evaluated: Mar 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:99270539
Last Evaluated: Mar 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:99270539
Last Evaluated: Mar 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:99270539
Last Evaluated: Mar 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:99270539
Expert Reviewed drug response
Normal
Gene:
UGT1A1
Variant:
c.-364C>T
rsID: rs887829
Ref Allele: C
Alt Allele: T
Freq: 35.4034%
CADD: 4.544
ClinVar Submissions (1)
Last Evaluated: Mar 23, 2018
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:234668570
Expert Reviewed drug response
Normal
Gene:
LOC100996325
Variant:
n.366+1469G>A
rsID: rs924607
Ref Allele: C
Alt Allele: T
Freq: 28.2149%
CADD: 0.172
ClinVar Submissions (1)
Last Evaluated: Feb 23, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 5:610093
Expert Reviewed drug response
Homo
Gene:
NAT2
Variant:
c.282C>T
(p.Tyr94=)
rsID: rs1041983
Ref Allele: C
Alt Allele: T
Freq: 39.7364%
CADD: 0.354
ClinVar Submissions (1)
Last Evaluated: Oct 27, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 8:18257795
Expert Reviewed drug response
Normal
Gene:
TP53
Variant:
c.215C>G
(p.Pro72Arg)
rsID: rs1042522
Ref Allele: G
Alt Allele: C
Freq: 45.7069%
CADD: 9.782
ClinVar Submissions (15)
Last Evaluated: Aug 18, 2017
Review Status: reviewed by expert panel
Number of Submitters: 15
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 17:7579472
OMIM Allelic Variant: 191170.0005
Last Evaluated: Aug 18, 2017
Review Status: reviewed by expert panel
Number of Submitters: 15
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 17:7579472
OMIM Allelic Variant: 191170.0005
Last Evaluated: Aug 18, 2017
Review Status: reviewed by expert panel
Number of Submitters: 15
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 17:7579472
OMIM Allelic Variant: 191170.0005
Last Evaluated: Aug 18, 2017
Review Status: reviewed by expert panel
Number of Submitters: 15
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 17:7579472
OMIM Allelic Variant: 191170.0005
Last Evaluated: Aug 18, 2017
Review Status: reviewed by expert panel
Number of Submitters: 15
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 17:7579472
OMIM Allelic Variant: 191170.0005
Last Evaluated: Aug 18, 2017
Review Status: reviewed by expert panel
Number of Submitters: 15
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 17:7579472
OMIM Allelic Variant: 191170.0005
Last Evaluated: Aug 18, 2017
Review Status: reviewed by expert panel
Number of Submitters: 15
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 17:7579472
OMIM Allelic Variant: 191170.0005
Last Evaluated: Aug 18, 2017
Review Status: reviewed by expert panel
Number of Submitters: 15
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 17:7579472
OMIM Allelic Variant: 191170.0005
Last Evaluated: Aug 18, 2017
Review Status: reviewed by expert panel
Number of Submitters: 15
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 17:7579472
OMIM Allelic Variant: 191170.0005
Last Evaluated: Aug 18, 2017
Review Status: reviewed by expert panel
Number of Submitters: 15
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 17:7579472
OMIM Allelic Variant: 191170.0005
Last Evaluated: Aug 18, 2017
Review Status: reviewed by expert panel
Number of Submitters: 15
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 17:7579472
OMIM Allelic Variant: 191170.0005
Low clinical importance, Uncertain pathogenic — This is a common variant was first reported as a polymorphism. It has since had mixed associations with cancer: Storey et al. conclude a 7x *increased* risk of HPV cancer for homozygotes vs hets, but Jones et al. find a 1.98x *decreased* risk for colorectal cancer. This variant may have significant impact on particular cancers, but it is unclear what effect it has on the overall burden of cancer.
Expert Reviewed drug response
Hetero
Gene:
ADRB2
Variant:
c.46A=
(p.Arg16=)
rsID: rs1042713
Ref Allele: G
Freq: 47.5639%
CADD: 16.37
ClinVar Submissions (1)
Last Evaluated: Oct 14, 2015
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 5:148206440
Last Evaluated: Oct 14, 2015
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 5:148206440
Expert Reviewed drug response
Hetero
Gene:
G6PD
Variant:
c.292G>A
(p.Val98Met)
rsID: rs1050828
Ref Allele: C
Alt Allele: T
Freq: 3.7616%uncommon
ClinVar Submissions (13)
Last Evaluated: Jun 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 13
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: X:153764217
OMIM Allelic Variant: 305900.0002
Last Evaluated: Jun 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 13
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: X:153764217
OMIM Allelic Variant: 305900.0002
Last Evaluated: Jun 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 13
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: X:153764217
OMIM Allelic Variant: 305900.0002
Last Evaluated: Jun 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 13
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: X:153764217
OMIM Allelic Variant: 305900.0002
Last Evaluated: Jun 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 13
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: X:153764217
OMIM Allelic Variant: 305900.0002
Last Evaluated: Jun 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 13
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: X:153764217
OMIM Allelic Variant: 305900.0002
Last Evaluated: Jun 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 13
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: X:153764217
OMIM Allelic Variant: 305900.0002
The data does not specify whether the genetic variant is autosomal recessive or autosomal dominant. For a definitive determination, refer to resources such as OMIM.
Expert Reviewed Clinically Significant drug response
Normal
Gene:
CHRNA3
Variant:
c.645C>T
(p.Tyr215=)
rsID: rs1051730
Ref Allele: G
Alt Allele: A
Freq: 16.8131%
CADD: 10.1
ClinVar Submissions (2)
Last Evaluated: Apr 01, 2015
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 15:78894339
OMIM Allelic Variant: 118503.0001
Last Evaluated: Apr 01, 2015
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 15:78894339
OMIM Allelic Variant: 118503.0001
Last Evaluated: Apr 01, 2015
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 15:78894339
OMIM Allelic Variant: 118503.0001
Expert Reviewed drug response
Hetero
Gene:
EPHX1
Variant:
c.337T>C
(p.Tyr113His)
rsID: rs1051740
Ref Allele: T
Alt Allele: C
Freq: 31.3299%
CADD: 28
ClinVar Submissions (2)
Last Evaluated: Sep 20, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:226019633
OMIM Allelic Variant: 132810.0001
Last Evaluated: Sep 20, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:226019633
OMIM Allelic Variant: 132810.0001
Insufficiently evaluated pharmacogenetic — This gene is involved in response to oxidative stress, and the 113H variant is associated with lower enzyme activity, apparently through disruption of protein stability rather than enzymatic function of the protein itself. Several studies have attempted to link this variant to cancer, lung disease, and other associations, but it is unclear which of these are results reproducible and validated.
Expert Reviewed drug response
Hetero
Gene:
DRD2
Variant:
c.811-83G>T
rsID: rs1076560
Ref Allele: C
Alt Allele: A
Freq: 22.9633%
CADD: 8.805
ClinVar Submissions (2)
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Last Evaluated: Aug 28, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:113283688
Last Evaluated: Aug 28, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:113283688
Expert Reviewed drug response
Normal
Gene:
GATM
Variant:
c.-394-272A>G
rsID: rs1346268
Ref Allele: T
Alt Allele: C
Freq: 45.0879%
CADD: 2.853
ClinVar Submissions (1)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 15:45673029
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 15:45673029
Expert Reviewed drug response
Normal
Gene:
HTR2C
Variant:
c.551-3008C>G
rsID: rs1414334
Ref Allele: C
Alt Allele: G
Freq: 19.1788%
ClinVar Submissions (2)
Last Evaluated: Mar 09, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: X:114138144
Clozapine is one of the most effective antipsychotics available in the treatment of schizophrenia and the only antipsychotic found to be effective in treatment-resistant schizophrenia. Clozapine is also used to reduce the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder. Compared to typical antipsychotics, clozapine is far less likely to cause movement disorders, known as extrapyramidal side effects, which include dystonia, akathisia, parkinsonism, and tardive dyskinesia. However, there are significant risks associated with clozapine therapy that limits its use to only the most severely ill patients who have not responded adequately to standard drug therapy. Most notably, because of the risk of clozapine-induced agranulocytosis, clozapine treatment requires monitoring of white blood counts and absolute neutrophil counts, and in the US, the FDA requires that patients receiving clozapine be enrolled in a computer-based registry. Clozapine is metabolized in the liver by the cytochrome P450 (CYP) system of enzymes. CYP1A2 is the main CYP isoform in clozapine metabolism and CYP1A2 activity is an important determinant of clozapine dose. Other CYP enzymes involved in clozapine metabolism include CYP2D6 and CYP3A4. Approximately 6-10% of Caucasians have reduced activity of CYP2D6 ("poor metabolizers"). These individuals may develop higher than expected plasma concentrations of clozapine with usual doses. The FDA-approved drug label for clozapine states that a dose reduction may be necessary in patients who are CYP2D6 poor metabolizers.
Last Evaluated: Mar 09, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: X:114138144
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Mar 09, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: X:114138144
Last Evaluated: Mar 09, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: X:114138144
Last Evaluated: Mar 09, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: X:114138144
Expert Reviewed drug response
Homo
Gene:
C8orf34
Variant:
c.736+8162C>G
rsID: rs1517114
Ref Allele: G
Alt Allele: C
Freq: 31.6494%
CADD: 0.075
ClinVar Submissions (1)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 8:69389217
Expert Reviewed drug response
Hetero
Gene:
CETP
Variant:
c.658+186C>A
rsID: rs1532624
Ref Allele: C
Alt Allele: A
Freq: 31.3099%
CADD: 4.829
ClinVar Submissions (1)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:57005479
Expert Reviewed drug response
Hetero
Gene:
-
Variant:
g.45328787C>T
rsID: rs1719247
Ref Allele: C
Alt Allele: T
Freq: 41.254%
CADD: 3.712
ClinVar Submissions (1)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 15:45620985
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 15:45620985
Expert Reviewed drug response
Normal
Gene:
NAT2
Variant:
c.590G>A
(p.Arg197Gln)
rsID: rs1799930
Ref Allele: G
Alt Allele: A
Freq: 26.4976%
CADD: 23.8
ClinVar Submissions (2)
Last Evaluated: Oct 27, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 8:18258103
OMIM Allelic Variant: 612182.0001
Last Evaluated: Oct 27, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 8:18258103
OMIM Allelic Variant: 612182.0001
Insufficiently evaluated pharmacogenetic — This allele characterizes the NAT2*6A haplotype which causes slow acetylation.
Expert Reviewed drug response
Normal
Gene:
OPRM1
Variant:
c.118A>G
(p.Asn40Asp)
rsID: rs1799971
Ref Allele: A
Alt Allele: G
Freq: 22.3442%
CADD: 24
ClinVar Submissions (2)
Last Evaluated: Apr 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 6:154360797
OMIM Allelic Variant: 600018.0001
Last Evaluated: Apr 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 6:154360797
OMIM Allelic Variant: 600018.0001
Last Evaluated: Apr 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 6:154360797
OMIM Allelic Variant: 600018.0001
Last Evaluated: Apr 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 6:154360797
OMIM Allelic Variant: 600018.0001
Last Evaluated: Apr 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 6:154360797
OMIM Allelic Variant: 600018.0001
Last Evaluated: Apr 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 6:154360797
OMIM Allelic Variant: 600018.0001
Last Evaluated: Apr 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 6:154360797
OMIM Allelic Variant: 600018.0001
Last Evaluated: Apr 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 6:154360797
OMIM Allelic Variant: 600018.0001
Last Evaluated: Apr 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 6:154360797
OMIM Allelic Variant: 600018.0001
Last Evaluated: Apr 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 6:154360797
OMIM Allelic Variant: 600018.0001
Last Evaluated: Apr 20, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 6:154360797
OMIM Allelic Variant: 600018.0001
Insufficiently evaluated pharmacogenetic — Better clinical outcome with ethanol and naltrexone.
Expert Reviewed drug response
Hetero
Gene:
DRD2
Variant:
c.-585A>G
rsID: rs1799978
Ref Allele: T
Alt Allele: C
Freq: 11.901%
CADD: 1.805
ClinVar Submissions (2)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Mar 09, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:113346351
Last Evaluated: Mar 09, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:113346351
Expert Reviewed drug response
Normal
Gene:
ANKK1;DRD2
Variant:
c.2137G>A
(p.Glu713Lys)
rsID: rs1800497
Ref Allele: G
Alt Allele: A
Freq: 32.5679%
CADD: 10.6
ClinVar Submissions (3)
Last Evaluated: May 24, 2018
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:113270828
OMIM Allelic Variant: 608774.0001
Last Evaluated: May 24, 2018
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:113270828
OMIM Allelic Variant: 608774.0001
Last Evaluated: May 24, 2018
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:113270828
OMIM Allelic Variant: 608774.0001
Clozapine is one of the most effective antipsychotics available in the treatment of schizophrenia and the only antipsychotic found to be effective in treatment-resistant schizophrenia. Clozapine is also used to reduce the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder. Compared to typical antipsychotics, clozapine is far less likely to cause movement disorders, known as extrapyramidal side effects, which include dystonia, akathisia, parkinsonism, and tardive dyskinesia. However, there are significant risks associated with clozapine therapy that limits its use to only the most severely ill patients who have not responded adequately to standard drug therapy. Most notably, because of the risk of clozapine-induced agranulocytosis, clozapine treatment requires monitoring of white blood counts and absolute neutrophil counts, and in the US, the FDA requires that patients receiving clozapine be enrolled in a computer-based registry. Clozapine is metabolized in the liver by the cytochrome P450 (CYP) system of enzymes. CYP1A2 is the main CYP isoform in clozapine metabolism and CYP1A2 activity is an important determinant of clozapine dose. Other CYP enzymes involved in clozapine metabolism include CYP2D6 and CYP3A4. Approximately 6-10% of Caucasians have reduced activity of CYP2D6 ("poor metabolizers"). These individuals may develop higher than expected plasma concentrations of clozapine with usual doses. The FDA-approved drug label for clozapine states that a dose reduction may be necessary in patients who are CYP2D6 poor metabolizers.
Last Evaluated: May 24, 2018
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:113270828
OMIM Allelic Variant: 608774.0001
Last Evaluated: May 24, 2018
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:113270828
OMIM Allelic Variant: 608774.0001
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: May 24, 2018
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:113270828
OMIM Allelic Variant: 608774.0001
Last Evaluated: May 24, 2018
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:113270828
OMIM Allelic Variant: 608774.0001
Last Evaluated: May 24, 2018
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:113270828
OMIM Allelic Variant: 608774.0001
Expert Reviewed drug response
Normal
Gene:
NQO1
Variant:
c.559C>T
(p.Pro187Ser)
rsID: rs1800566
Ref Allele: G
Alt Allele: A
Freq: 28.8938%
CADD: 24.8
ClinVar Submissions (3)
Last Evaluated: Mar 10, 2016
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:69745145
OMIM Allelic Variant: 125860.0001
Last Evaluated: Mar 10, 2016
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:69745145
OMIM Allelic Variant: 125860.0001
Last Evaluated: Mar 10, 2016
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:69745145
OMIM Allelic Variant: 125860.0001
Last Evaluated: Mar 10, 2016
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:69745145
OMIM Allelic Variant: 125860.0001
Lung cancer is the leading cause of cancer deaths in the U.S. and worldwide. The 2 major forms of lung cancer are nonsmall cell lung cancer and small cell lung cancer (see 182280), which account for 85% and 15% of all lung cancers, respectively. Nonsmall cell lung cancer can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. Cigarette smoking causes all types of lung cancer, but it is most strongly linked with small cell lung cancer and squamous cell carcinoma. Adenocarcinoma is the most common type in patients who have never smoked. Nonsmall cell lung cancer is often diagnosed at an advanced stage and has a poor prognosis (summary by Herbst et al., 2008).
Last Evaluated: Mar 10, 2016
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:69745145
OMIM Allelic Variant: 125860.0001
The individual has two copies of the variant, which suggests they may manifest the associated condition or trait. However, it's important to conduct thorough research before drawing definitive conclusions.
Expert Reviewed Clinically Significant drug response
Homo
Gene:
TNF
Variant:
c.-488G>A
rsID: rs1800629
Ref Allele: G
Alt Allele: A
Freq: 9.0256%
CADD: 3.923
ClinVar Submissions (1)
Last Evaluated: Jun 07, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 6:31543031
Last Evaluated: Jun 07, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 6:31543031
Last Evaluated: Jun 07, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 6:31543031
Last Evaluated: Jun 07, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 6:31543031
Expert Reviewed drug response
Normal
Gene:
UMPS
Variant:
c.638G>C
(p.Gly213Ala)
rsID: rs1801019
Ref Allele: G
Alt Allele: C
Freq: 18.5903%
CADD: 9.021
ClinVar Submissions (4)
Orotic aciduria is a rare autosomal recessive disorder characterized by megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy, and most cases appear to have a good prognosis. A minority of cases have additional features, particularly congenital malformations and immune deficiencies, which may adversely affect this prognosis (summary by Webster et al., 2001). Bailey (2009) stated that only 2 cases of orotic aciduria without megaloblastic anemia (OAWA) had been reported.
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 3:124456742
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 3:124456742
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 3:124456742
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 3:124456742
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 3:124456742
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 3:124456742
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 3:124456742
Expert Reviewed drug response
Normal
Gene:
FCGR2A
Variant:
c.497A>G
(p.His166Arg)
rsID: rs1801274
Ref Allele: A
Alt Allele: G
Freq: 44.1693%
CADD: 0.979
ClinVar Submissions (3)
Last Evaluated: Mar 28, 2016
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:161479745
OMIM Allelic Variant: 146790.0001
Last Evaluated: Mar 28, 2016
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:161479745
OMIM Allelic Variant: 146790.0001
Last Evaluated: Mar 28, 2016
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:161479745
OMIM Allelic Variant: 146790.0001
Last Evaluated: Mar 28, 2016
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:161479745
OMIM Allelic Variant: 146790.0001
Last Evaluated: Mar 28, 2016
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:161479745
OMIM Allelic Variant: 146790.0001
Expert Reviewed drug response
Homo
Gene:
MTRR
Variant:
c.66A>G
(p.Ile22Met)
rsID: rs1801394
Ref Allele: A
Alt Allele: G
Freq: 36.4217%
CADD: 20.9
ClinVar Submissions (6)
Last Evaluated: Jan 30, 2018
Review Status: reviewed by expert panel
Number of Submitters: 6
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 5:7870973
OMIM Allelic Variant: 602568.0003
Last Evaluated: Jan 30, 2018
Review Status: reviewed by expert panel
Number of Submitters: 6
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 5:7870973
OMIM Allelic Variant: 602568.0003
Last Evaluated: Jan 30, 2018
Review Status: reviewed by expert panel
Number of Submitters: 6
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 5:7870973
OMIM Allelic Variant: 602568.0003
Last Evaluated: Jan 30, 2018
Review Status: reviewed by expert panel
Number of Submitters: 6
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 5:7870973
OMIM Allelic Variant: 602568.0003
Last Evaluated: Jan 30, 2018
Review Status: reviewed by expert panel
Number of Submitters: 6
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 5:7870973
OMIM Allelic Variant: 602568.0003
Last Evaluated: Jan 30, 2018
Review Status: reviewed by expert panel
Number of Submitters: 6
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 5:7870973
OMIM Allelic Variant: 602568.0003
Low clinical importance, Likely pathogenic — This common variant (HapMap allele frequency of 31.3%) in a protein involved in folate (B9) and cobalamin (B12) metabolism and is often reported as "MTRR I22M" (an alternative transcript position). Mothers homozygous for this variant are associated with having around a increased chance of a child with Down syndrome (risk of 0.4%, average risk in population is 0.25%). Notably, age plays a far larger role in the rate of Down syndrome (risk is 4.5% for a mother 45-years-of-age), and it is unknown how this variant may combine with the effect of age. There are conflicting reports associating this variant with incidence of neural tube defects, possibly when combined with MTHFR A222V.
Expert Reviewed drug response
Hetero
Gene:
ACYP2
Variant:
c.404+29374G>A
rsID: rs1872328
Ref Allele: G
Alt Allele: A
Freq: 7.1685%
CADD: 0.897
ClinVar Submissions (1)
Last Evaluated: Dec 07, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:54395259
Expert Reviewed drug response
Normal
Gene:
GRIK4
Variant:
c.83-10039T>C
rsID: rs1954787
Ref Allele: T
Alt Allele: C
Freq: 49.7804%
CADD: 3.797
ClinVar Submissions (2)
Last Evaluated: Mar 09, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:120663363
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Mar 09, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:120663363
Expert Reviewed drug response
Homo
Gene:
CYP4F2
Variant:
c.1297G>A
(p.Val433Met)
rsID: rs2108622
Ref Allele: C
Alt Allele: T
Freq: 23.6821%
CADD: 24
ClinVar Submissions (1)
Last Evaluated: Apr 06, 2018
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:15990431
Last Evaluated: Apr 06, 2018
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:15990431
Last Evaluated: Apr 06, 2018
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:15990431
Last Evaluated: Apr 06, 2018
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:15990431
Insufficiently evaluated pharmacogenetic — Requires 1mg/day greater dose of warfarin.
Expert Reviewed drug response
Normal
Gene:
TMEM43;XPC
Variant:
c.2815C>A
(p.Gln939Lys)
rsID: rs2228001
Ref Allele: G
Alt Allele: T
Freq: 31.5296%
CADD: 18.95
ClinVar Submissions (4)
Arrhythmogenic right ventricular cardiomyopathy (ARVC) – previously referred to as arrhythmogenic right ventricular dysplasia (ARVD) – is characterized by progressive fibrofatty replacement of the myocardium that predisposes to ventricular tachycardia and sudden death in young individuals and athletes. It primarily affects the right ventricle, and it may also involve the left ventricle. The presentation of disease is highly variable even within families, and some affected individuals may not meet established clinical criteria. The mean age at diagnosis is 31 years (±13; range: 4-64 years).
Last Evaluated: May 03, 2017
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 3:14187449
Xeroderma pigmentosum (XP) is characterized by: Sun sensitivity (severe sunburn with blistering, persistent erythema on minimal sun exposure in ~60% of affected individuals), with marked freckle-like pigmentation of the face before age two years in most affected individuals; Sunlight-induced ocular involvement (photophobia, keratitis, atrophy of the skin of the lids); Greatly increased risk of sunlight-induced cutaneous neoplasms (basal cell carcinoma, squamous cell carcinoma, melanoma). Approximately 25% of affected individuals have neurologic manifestations (acquired microcephaly, diminished or absent deep tendon stretch reflexes, progressive sensorineural hearing loss, and progressive cognitive impairment). The most common causes of death are skin cancer, neurologic degeneration, and internal cancer. The median age at death in persons with XP with neurodegeneration (29 years) was found to be younger than that in persons with XP without neurodegeneration (37 years).
Last Evaluated: May 03, 2017
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 3:14187449
Last Evaluated: May 03, 2017
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 3:14187449
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: May 03, 2017
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 3:14187449
Expert Reviewed drug response
Homo
Gene:
ABCG2
Variant:
c.421C>A
(p.Gln141Lys)
rsID: rs2231142
Ref Allele: G
Alt Allele: T
Freq: 11.9409%
CADD: 22.3
ClinVar Submissions (3)
Last Evaluated: Feb 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 4:89052323
OMIM Allelic Variant: 603756.0007
Last Evaluated: Feb 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 4:89052323
OMIM Allelic Variant: 603756.0007
Last Evaluated: Feb 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 4:89052323
OMIM Allelic Variant: 603756.0007
Last Evaluated: Feb 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 4:89052323
OMIM Allelic Variant: 603756.0007
Last Evaluated: Feb 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 4:89052323
OMIM Allelic Variant: 603756.0007
Insufficiently evaluated pharmacogenetic — Significantly altered kintetics and increase plasma AUC with diflomotecan and rosuvastatin.
Expert Reviewed drug response
Normal
Gene:
HAS3
Variant:
c.279A>G
(p.Ala93=)
rsID: rs2232228
Ref Allele: A
Alt Allele: G
Freq: 34.2252%
CADD: 15.71
ClinVar Submissions (1)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:69143577
Expert Reviewed drug response
Hetero
Gene:
EPHX1
Variant:
c.416A>G
(p.His139Arg)
rsID: rs2234922
Ref Allele: A
Alt Allele: G
Freq: 21.5455%
CADD: 8.51
ClinVar Submissions (2)
Last Evaluated: Jan 20, 2016
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:226026406
OMIM Allelic Variant: 132810.0002
Last Evaluated: Jan 20, 2016
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:226026406
OMIM Allelic Variant: 132810.0002
Expert Reviewed drug response
Hetero
Gene:
CYP2B6
Variant:
c.785A>G
(p.Lys262Arg)
rsID: rs2279343
Ref Allele: A
Alt Allele: G
CADD: 0.07
ClinVar Submissions (4)
Highly active antiretroviral therapy (HAART) has reduced mortality associated with acquired immunodeficiency syndrome (AIDS; see 609423) by at least 70%. Efavirenz is a non-nucleoside reverse transcriptase inhibitor that is frequently prescribed with 2 nucleoside reverse transcriptase inhibitors as initial therapy for human immunodeficiency virus (HIV) infection. However, during the first weeks of therapy, up to half of patients who receive efavirenz experience CNS side effects, including dizziness, insomnia, impaired concentration, somnolence, and abnormal dreams. Severe depression, aggressive behavior, and paranoid or manic reactions may also occur, and such side effects may reflect varying efavirenz plasma concentrations. Plasma clearance of efavirenz appears slower in African Americans than in European Americans, and studies have suggested earlier virologic failure on efavirenz for both African Americans and Hispanics compared with European Americans. Efavirenz is metabolized primarily by hepatic CYP2B6, with some involvement of CYP3A (CYP3A4; 124010) (summary by Haas et al., 2004).
Last Evaluated: Mar 22, 2016
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:41515263
OMIM Allelic Variant: 123930.0002
Last Evaluated: Mar 22, 2016
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:41515263
OMIM Allelic Variant: 123930.0002
Expert Reviewed drug response
Hetero
Gene:
CYP2B6
Variant:
c.823-197T>C
rsID: rs2279345
Ref Allele: T
Alt Allele: C
Freq: 26.5176%
CADD: 0.382
ClinVar Submissions (1)
Last Evaluated: Dec 20, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:41515702
Expert Reviewed drug response
Homo
Gene:
ADORA2A
Variant:
c.-275+1797C>T
rsID: rs2298383
Ref Allele: C
Alt Allele: T
Freq: 40.0559%
CADD: 1.152
ClinVar Submissions (1)
Last Evaluated: Dec 20, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 22:24825511
Expert Reviewed drug response
Hetero
Gene:
VKORC1
Variant:
c.283+837T>C
rsID: rs2359612
Ref Allele: A
Alt Allele: G
Freq: 39.0375%
CADD: 6.613
ClinVar Submissions (1)
Last Evaluated: Dec 07, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:31103796
Expert Reviewed drug response
Normal
Gene:
CYP3A4
Variant:
c.-392G>A
rsID: rs2740574
Ref Allele: C
Alt Allele: T
Freq: 23.0831%
CADD: 5.538
ClinVar Submissions (2)
Last Evaluated: Feb 23, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:99382096
OMIM Allelic Variant: 124010.0001
Last Evaluated: Feb 23, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:99382096
OMIM Allelic Variant: 124010.0001
Last Evaluated: Feb 23, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:99382096
OMIM Allelic Variant: 124010.0001
Expert Reviewed drug response
Homo
Gene:
VKORC1
Variant:
c.173+324T>G
rsID: rs2884737
Ref Allele: A
Alt Allele: C
Freq: 9.1454%
CADD: 2.039
ClinVar Submissions (1)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:31105554
Expert Reviewed drug response
Hetero
Gene:
-
Variant:
g.207629510T>C
rsID: rs2952768
Ref Allele: T
Alt Allele: C
Freq: 38.6382%
CADD: 6.626
ClinVar Submissions (1)
Last Evaluated: Oct 14, 2015
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:208494234
Last Evaluated: Oct 14, 2015
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:208494234
Last Evaluated: Oct 14, 2015
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:208494234
Last Evaluated: Oct 14, 2015
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:208494234
Last Evaluated: Oct 14, 2015
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:208494234
Last Evaluated: Oct 14, 2015
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:208494234
Expert Reviewed drug response
Hetero
Gene:
CYP2B6
Variant:
c.516G>T
(p.Gln172His)
rsID: rs3745274
Ref Allele: G
Alt Allele: T
Freq: 31.5695%
CADD: 0.002
ClinVar Submissions (2)
Highly active antiretroviral therapy (HAART) has reduced mortality associated with acquired immunodeficiency syndrome (AIDS; see 609423) by at least 70%. Efavirenz is a non-nucleoside reverse transcriptase inhibitor that is frequently prescribed with 2 nucleoside reverse transcriptase inhibitors as initial therapy for human immunodeficiency virus (HIV) infection. However, during the first weeks of therapy, up to half of patients who receive efavirenz experience CNS side effects, including dizziness, insomnia, impaired concentration, somnolence, and abnormal dreams. Severe depression, aggressive behavior, and paranoid or manic reactions may also occur, and such side effects may reflect varying efavirenz plasma concentrations. Plasma clearance of efavirenz appears slower in African Americans than in European Americans, and studies have suggested earlier virologic failure on efavirenz for both African Americans and Hispanics compared with European Americans. Efavirenz is metabolized primarily by hepatic CYP2B6, with some involvement of CYP3A (CYP3A4; 124010) (summary by Haas et al., 2004).
Last Evaluated: Apr 26, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:41512841
OMIM Allelic Variant: 123930.0001
Last Evaluated: Apr 26, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:41512841
OMIM Allelic Variant: 123930.0001
Last Evaluated: Apr 26, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:41512841
OMIM Allelic Variant: 123930.0001
Last Evaluated: Apr 26, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:41512841
OMIM Allelic Variant: 123930.0001
Last Evaluated: Apr 26, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:41512841
OMIM Allelic Variant: 123930.0001
Expert Reviewed drug response
Hetero
Gene:
PTGFR
Variant:
c.-562T>C
rsID: rs3753380
Ref Allele: T
Alt Allele: C
Freq: 21.7652%
CADD: 3.036
ClinVar Submissions (1)
Last Evaluated: Jan 21, 2015
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:78956432
Expert Reviewed drug response
Homo
Gene:
HTR2C
Variant:
c.-850C>T
rsID: rs3813929
Ref Allele: C
Alt Allele: T
Freq: 13.4834%
ClinVar Submissions (1)
Last Evaluated: Dec 20, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: X:113818520
Expert Reviewed drug response
Homo
Gene:
DPYD
Variant:
c.1905+1G>A
rsID: rs3918290
Ref Allele: C
Alt Allele: T
Freq: 0.2995%rare
CADD: 31
ClinVar Submissions (14)
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). Levy et al. (2009) provided a general review of autism and autism spectrum disorder, including epidemiology, characteristics of the disorder, diagnosis, neurobiologic hypotheses for the etiology, genetics, and treatment options. Genetic Heterogeneity of Autism Autism is considered to be a complex multifactorial disorder involving many genes. Accordingly, several loci have been identified, some or all of which may contribute to the phenotype. Included in this entry is AUTS1, which has been mapped to chromosome 7q22. Other susceptibility loci include AUTS3 (608049), which maps to chromosome 13q14; AUTS4 (608636), which maps to chromosome 15q11; AUTS6 (609378), which maps to chromosome 17q11; AUTS7 (610676), which maps to chromosome 17q21; AUTS8 (607373), which maps to chromosome 3q25-q27; AUTS9 (611015), which maps to chromosome 7q31; AUTS10 (611016), which maps to chromosome 7q36; AUTS11 (610836), which maps to chromosome 1q41; AUTS12 (610838), which maps to chromosome 21p13-q11; AUTS13 (610908), which maps to chromosome 12q14; AUTS14A (611913), which has been found in patients with a deletion of a region of 16p11.2; AUTS14B (614671), which has been found in patients with a duplication of a region of 16p11.2; AUTS15 (612100), associated with mutation in the CNTNAP2 gene (604569) on chromosome 7q35-q36; AUTS16 (613410), associated with mutation in the SLC9A9 gene (608396) on chromosome 3q24; AUTS17 (613436), associated with mutation in the SHANK2 gene (603290) on chromosome 11q13; AUTS18 (615032), associated with mutation in the CHD8 gene (610528) on chromosome 14q11; and AUTS19, associated with mutation in the EIF4E gene (133440) on chromosome 4q23. (NOTE: the symbol 'AUTS2' has been used to refer to a gene on chromosome 7q11 (KIAA0442; 607270) and therefore is not used as a part of this autism locus series.) There are several X-linked forms of autism susceptibility: AUTSX1 (300425), associated with mutations in the NLGN3 gene (300336); AUTSX2 (300495), associated with mutations in NLGN4 (300427); AUTSX3 (300496), associated with mutations in MECP2 (300005); AUTSX4 (300830), associated with variation in the region on chromosome Xp22.11 containing the PTCHD1 gene (300828); AUTSX5 (300847), associated with mutations in the RPL10 gene (312173); and AUTSX6 (300872), associated with mutation in the TMLHE gene (300777). A locus on chromosome 2q (606053) associated with a phenotype including intellectual disability and speech deficits was formerly designated AUTS5. Folstein and Rosen-Sheidley (2001) reviewed the genetics of autism.
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
Increased volume and globular shape of the anteroinferior aspect of the nose.
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
Bending or curvature of a fifth toe in the tibial direction (i.e., towards the big toe).
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
A notable change in cognitive function.
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
5-fluorouracil is a chemotherapeutic agent, and a member of the fluoropyrimidine group of substances. It is mainly used to treat solid tumors, such as colorectal, breast and aerodigestive cancers. Dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene) is the rate-limiting enzyme for fluoropyrimidine metabolism and is therefore responsible for the detoxification of these types of drugs. Patients who are homozygous for variants in DPYD that lead to a non-functional protein, such as *2A or *13, have a high risk of severe or fatal drug toxicities and may benefit from receiving an alternative chemotherapeutic drug. Patients heterozygous for these variants also have an increased risk for drug toxicities, and reduced dosing is recommended for these individuals. Guidelines regarding the use of pharmacogenomic tests in dosing for 5-fluorouracil have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website (http://www.pharmgkb.org/drug/PA128406956).
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
A skeletal deformity characterized by an unusually prominent forehead. Causes include acromegaly, Hurler syndrome, Silver-Russell syndrome, and thalassemia major.
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age. [DDD:hvfirth, HPO:sdoelken]
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
A deformity characterized by lateral deviation of the great toe.
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
Hirschsprung disease (HSCR), or congenital intestinal aganglionosis, is a birth defect characterized by complete absence of neuronal ganglion cells from a portion of the intestinal tract. The aganglionic segment includes the distal rectum and a variable length of contiguous proximal intestine. In 80% of individuals, aganglionosis is restricted to the rectosigmoid colon (short-segment disease); in 15%-20%, aganglionosis extends proximal to the sigmoid colon (long-segment disease); in about 5%, aganglionosis affects the entire large intestine (total colonic aganglionosis). Rarely, the aganglionosis extends into the small bowel or even more proximally to encompass the entire bowel (total intestinal aganglionosis). HSCR is considered a neurocristopathy, a disorder of cells and tissues derived from the neural crest, and may occur as an isolated finding or as part of a multisystem disorder. Affected infants frequently present in the first two months of life with symptoms of impaired intestinal motility such as failure to pass meconium within the first 48 hours of life, constipation, emesis, abdominal pain or distention, and occasionally diarrhea. However, because the initial diagnosis of HSCR may be delayed until late childhood or adulthood, HSCR should be considered in anyone with lifelong severe constipation. Individuals with HSCR are at risk for enterocolitis and/or potentially lethal intestinal perforation.
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
Profound mental retardation is defined as an intelligence quotient (IQ) below 20. [HPO:probinson]
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
Macroglossia is an abnormal enlargement of the tongue. It is commonly observed with type 2 glycogen storage disease (232300), neurofibromatosis (162200), congenital hypothyroidism, and the Beckwith-Wiedemann syndrome (130650).
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
Abnormal prominence of the chin related to increased length of the mandible.
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
A profound delay in the achievement of motor or mental milestones in the domains of development of a child.
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder."
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
A toe that appears disproportionately short compared to the foot.
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
Abnormal reduction in length affecting all phalanges.
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
A type of stenosis of the external auditory meatus in which the opening of the external auditory meatus appears as a vertical slit.
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
Increased thickness of the lower lip, leading to a prominent appearance of the lower lip. The height of the vermilion of the lower lip in the midline is more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the lower lip in the frontal view (subjective). [HPO:curators, pmid:19125428]
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
Increased spaces (diastemata) between most of the teeth in the same dental arch.
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 14
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97915614
OMIM Allelic Variant: 612779.0001
This individual has one copy of the genetic mutation, and because the condition(s) are autosomal dominant, they may manifest the condition rather than just being a carrier. However, it's important to conduct thorough research before drawing definitive conclusions.
Expert Reviewed Clinically Significant drug response
Normal
Gene:
UGT1A1
Variant:
UGT1A1*6
rsID: rs4148323
Ref Allele: G
Freq: 3.4345%uncommon
CADD: 23.1
ClinVar Submissions (8)
Last Evaluated: Apr 04, 2018
Review Status: reviewed by expert panel
Number of Submitters: 8
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:234669144
OMIM Allelic Variant: 191740.0016
The hereditary hyperbilirubinemias (Wolkoff et al., 1983) include (1) those resulting in predominantly unconjugated hyperbilirubinemia: Gilbert or Arias syndrome, Crigler-Najjar syndrome type I (218800), and Crigler-Najjar syndrome type II (606785); and (2) those resulting in predominantly conjugated hyperbilirubinemia: Dubin-Johnson syndrome (237500), Rotor syndrome (237450), and several forms of intrahepatic cholestasis (147480, 211600, 214950, 243300). Detailed studies show that patients with Gilbert syndrome have reduced activity of bilirubin glucuronosyltransferase (Bosma et al., 1995, Koiwai et al., 1995). Genetic Heterogeneity of Hyperbilirubinemia See also Crigler-Najjar syndrome type I (HBLRCN1; 218800), Crigler-Najjar syndrome type II (HBLRCN2; 606785), and transient familial neonatal hyperbilirubinemia (HBLRTFN; 237900), all caused by mutation in the UGT1A1 gene (191740) on chromosome 2q37; Dubin-Johnson syndrome (DJS, HBLRDJ; 237500), caused by mutation in the ABCC2 gene (601107) on chromosome 10q24; and Rotor syndrome (HBLRR; 237450), caused by digenic mutation in the SLCO1B1 (604843) and SLCOB3 (605495) genes, both on chromosome 12p.
Last Evaluated: Apr 04, 2018
Review Status: reviewed by expert panel
Number of Submitters: 8
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:234669144
OMIM Allelic Variant: 191740.0016
Irinotecan (brand name Camptosar) is a topoisomerase I inhibitor widely used in the treatment of cancer. It is most frequently used in combination with other drugs to treat advanced or metastatic colorectal cancer. However, irinotecan therapy is associated with a high incidence of toxicity, including severe neutropenia and diarrhea. Irinotecan is converted in the body to an active metabolite known as SN-38, which is then inactivated and detoxified by a UDP-glucuronosyltransferase (UGT) enzyme encoded by the UGT1A1 gene. The UGT enzymes are responsible for glucuronidation, a process that transforms lipophilic metabolites into water-soluble metabolites that can be excreted from the body. The risk of irinotecan toxicity increases with genetic variants associated with reduced UGT enzyme activity, such as UGT1A1*28. The presence of this variant results in reduced excretion of irinotecan metabolites, which leads to increased active irinotecan metabolites in the blood. Approximately 10% of North Americans carry 2 copies of the UGT1A1*28 allele (homozygous, UGT1A1 *28/*28), and are more likely to develop neutropenia following irinotecan therapy. The FDA-approved drug label for irinotecan states that “when administered as a single-agent, a reduction in the starting dose by at least one level of irinotecan hydrochloride injection should be considered for patients known to be homozygous for the UGT1A1*28 allele. However, the precise dose reduction in this patient population is not known and subsequent dose modifications should be considered based on individual patient tolerance to treatment”. The Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Association for the Advancement of Pharmacy (KNMP) recommends starting with 70% of the standard dose for homozygous carriers of the UGT1A1*28 allele. If the patient tolerates this initial dose, the dose can be increased guided by the neutrophil count. They state that no action is needed for heterozygous carriers of the UGT1A1*28 allele (e.g., UGT1A1 *1/*28). In addition, the French National Network of Pharmacogenetics (RNPGx) has proposed a decision tree for guiding irinotecan prescribing based on the UGT1A1 genotype and irinotecan dose.
Last Evaluated: Apr 04, 2018
Review Status: reviewed by expert panel
Number of Submitters: 8
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:234669144
OMIM Allelic Variant: 191740.0016
Last Evaluated: Apr 04, 2018
Review Status: reviewed by expert panel
Number of Submitters: 8
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:234669144
OMIM Allelic Variant: 191740.0016
Last Evaluated: Apr 04, 2018
Review Status: reviewed by expert panel
Number of Submitters: 8
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:234669144
OMIM Allelic Variant: 191740.0016
Last Evaluated: Apr 04, 2018
Review Status: reviewed by expert panel
Number of Submitters: 8
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:234669144
OMIM Allelic Variant: 191740.0016
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Apr 04, 2018
Review Status: reviewed by expert panel
Number of Submitters: 8
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:234669144
OMIM Allelic Variant: 191740.0016
This individual has one copy of the genetic mutation, and because it's autosomal recessive, they are likely a carrier rather than manifesting the condition. Interpretation of carrier status should be backed by thorough research.
Expert Reviewed Clinically Significant drug response
Normal
Gene:
SLCO1B1
Variant:
c.-910G>A
rsID: rs4149015
Ref Allele: G
Alt Allele: A
Freq: 5.4713%
CADD: 0.546
ClinVar Submissions (1)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 12:21283322
Expert Reviewed drug response
Normal
Gene:
SLCO1B1
Variant:
c.521T>C
(p.Val174Ala)
rsID: rs4149056
Ref Allele: T
Alt Allele: C
Freq: 8.766%
CADD: 22.1
ClinVar Submissions (5)
Last Evaluated: May 21, 2018
Review Status: reviewed by expert panel
Number of Submitters: 5
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 12:21331549
Last Evaluated: May 21, 2018
Review Status: reviewed by expert panel
Number of Submitters: 5
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 12:21331549
Last Evaluated: May 21, 2018
Review Status: reviewed by expert panel
Number of Submitters: 5
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 12:21331549
Last Evaluated: May 21, 2018
Review Status: reviewed by expert panel
Number of Submitters: 5
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 12:21331549
Last Evaluated: May 21, 2018
Review Status: reviewed by expert panel
Number of Submitters: 5
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 12:21331549
Last Evaluated: May 21, 2018
Review Status: reviewed by expert panel
Number of Submitters: 5
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 12:21331549
Last Evaluated: May 21, 2018
Review Status: reviewed by expert panel
Number of Submitters: 5
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 12:21331549
Last Evaluated: May 21, 2018
Review Status: reviewed by expert panel
Number of Submitters: 5
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 12:21331549
Last Evaluated: May 21, 2018
Review Status: reviewed by expert panel
Number of Submitters: 5
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 12:21331549
Insufficiently evaluated pharmacogenetic — Increased plasma AUC with repaglinide.
Expert Reviewed drug response
Normal
Gene:
NEDD4L
Variant:
c.24G>A
(p.Gln8=)
rsID: rs4149601
Ref Allele: G
Alt Allele: A
Freq: 27.6158%
CADD: 10.52
ClinVar Submissions (1)
Last Evaluated: Apr 07, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 18:55816791
Last Evaluated: Apr 07, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 18:55816791
Expert Reviewed drug response
Normal
Gene:
CYP2C19
Variant:
c.681G>A
(p.Pro227=)
rsID: rs4244285
Ref Allele: G
Alt Allele: A
Freq: 22.1446%
CADD: 0.075
ClinVar Submissions (4)
Clopidogrel is a thienopyridine antiplatelet agent that prevents platelet activation and aggregation by irreversibly inhibiting the P2Y12 ADP receptors. As a pro-drug, clopidogrel requires hepatic biotransformation to form an active metabolite. This conversion is composed of two sequential oxidative steps, which involve cytochrome P450-2C19 (CYP2C19) and other enzymes. Genetic variants in CYP2C19 such as CYP2C19*2, along with other genetic and non-genetic factors, are known to influence variability in clopidogrel response. Specific CYP2C19 variants impair formation of the active clopidogrel metabolite, which results in reduced platelet inhibition. Among clopidogrel-treated patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention (PCI), patients with specific variants in the CYP2C19 gene might be at increased risk for serious adverse cardiovascular events and may benefit from an alternative antiplatelet therapy as compared to patients without these variants. Guidelines regarding the use of pharmacogenomic tests in dosing for clopidogrel have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website.
Last Evaluated: Aug 07, 2018
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96541616
OMIM Allelic Variant: 124020.0001
Last Evaluated: Aug 07, 2018
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96541616
OMIM Allelic Variant: 124020.0001
Last Evaluated: Aug 07, 2018
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96541616
OMIM Allelic Variant: 124020.0001
Last Evaluated: Aug 07, 2018
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96541616
OMIM Allelic Variant: 124020.0001
Last Evaluated: Aug 07, 2018
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96541616
OMIM Allelic Variant: 124020.0001
Last Evaluated: Aug 07, 2018
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96541616
OMIM Allelic Variant: 124020.0001
Last Evaluated: Aug 07, 2018
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96541616
OMIM Allelic Variant: 124020.0001
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Aug 07, 2018
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96541616
OMIM Allelic Variant: 124020.0001
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Aug 07, 2018
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96541616
OMIM Allelic Variant: 124020.0001
Insufficiently evaluated pharmacogenetic — This variant defines the CYP2C19*2 haplotype and is associated with diminished response of clopidogrel (plavix). Compared to individuals who do not have this variant, carriers of this variant are more likely to have a major adverse cardiovascular event despite treatment with clopidogrel.
Expert Reviewed drug response
Homo
Gene:
EGF
Variant:
c.-382A>G
rsID: rs4444903
Ref Allele: A
Alt Allele: G
Freq: 39.4768%
CADD: 11.57
ClinVar Submissions (2)
Last Evaluated: Feb 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 4:110834110
Last Evaluated: Feb 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 4:110834110
Expert Reviewed drug response
Normal
Gene:
COQ2
Variant:
c.779-1022C>G
rsID: rs4693075
Ref Allele: G
Alt Allele: C
Freq: 33.9856%
CADD: 1.453
ClinVar Submissions (1)
Last Evaluated: Oct 14, 2015
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 4:84192168
Last Evaluated: Oct 14, 2015
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 4:84192168
Last Evaluated: Oct 14, 2015
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 4:84192168
Expert Reviewed drug response
Hetero
Gene:
CYP2B6
Variant:
c.485-18C>T
rsID: rs4803419
Ref Allele: C
Alt Allele: T
Freq: 28.9137%
CADD: 4.765
ClinVar Submissions (1)
Last Evaluated: Dec 11, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:41512792
Expert Reviewed drug response
Hetero
Gene:
CYP2C9
Variant:
c.820-6326A>C
rsID: rs4917639
Ref Allele: A
Alt Allele: C
Freq: 16.3938%
CADD: 2.4
ClinVar Submissions (1)
Last Evaluated: Feb 24, 2015
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96725535
Expert Reviewed drug response
Normal
Gene:
CYP2C19
Variant:
c.636G>A
(p.Trp212Ter)
rsID: rs4986893
Ref Allele: G
Alt Allele: A
Freq: 1.4177%uncommon
CADD: 35
ClinVar Submissions (3)
Last Evaluated: Aug 17, 2017
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96540410
OMIM Allelic Variant: 124020.0003
Last Evaluated: Aug 17, 2017
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96540410
OMIM Allelic Variant: 124020.0003
Last Evaluated: Aug 17, 2017
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96540410
OMIM Allelic Variant: 124020.0003
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Aug 17, 2017
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96540410
OMIM Allelic Variant: 124020.0003
Insufficiently evaluated pharmacogenetic — CYP2C19*3 allele. Poor metabolism of Mephenytoin, poor metabolism of Proguanil (FDA approved).
Expert Reviewed drug response
Normal
Gene:
TANC1
Variant:
c.-15-22495C>T
rsID: rs6432512
Ref Allele: C
Alt Allele: T
Freq: 15.8546%
CADD: 0.084
ClinVar Submissions (1)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:159899913
Expert Reviewed drug response
Normal
Gene:
DPP6
Variant:
c.52-71279T>C
rsID: rs6977820
Ref Allele: T
Alt Allele: C
Freq: 42.2724%
CADD: 6.993
ClinVar Submissions (1)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:154072020
Expert Reviewed drug response
Hetero
Gene:
COL22A1
Variant:
c.658+5484G>A
rsID: rs6988229
Ref Allele: C
Alt Allele: T
Freq: 23.8219%
CADD: 2.477
ClinVar Submissions (1)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 8:139884509
Expert Reviewed drug response
Normal
Gene:
ITPA
Variant:
c.124+21A>C
rsID: rs7270101
Ref Allele: A
Alt Allele: C
Freq: 5.9105%
CADD: 13.34
ClinVar Submissions (2)
Last Evaluated: Apr 26, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 20:3193893
OMIM Allelic Variant: 147520.0002
Last Evaluated: Apr 26, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 20:3193893
OMIM Allelic Variant: 147520.0002
Last Evaluated: Apr 26, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 20:3193893
OMIM Allelic Variant: 147520.0002
Expert Reviewed drug response
Normal
Gene:
YEATS4
Variant:
g.69430244C>T
rsID: rs7297610
Ref Allele: C
Alt Allele: T
Freq: 11.5815%
CADD: 2.977
ClinVar Submissions (1)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 12:69824024
Expert Reviewed drug response
Normal
Gene:
TANC1
Variant:
c.-15-22919G>T
rsID: rs7582141
Ref Allele: G
Alt Allele: T
Freq: 15.5351%
CADD: 1.953
ClinVar Submissions (1)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:159899489
Expert Reviewed drug response
Normal
Gene:
SEMA3C
Variant:
c.103+13883A>G
rsID: rs7779029
Ref Allele: T
Alt Allele: C
Freq: 16.8331%
CADD: 0.165
ClinVar Submissions (1)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:80532112
Expert Reviewed drug response
Hetero
Gene:
CRHR2
Variant:
c.-166-546T>A
rsID: rs7793837
Ref Allele: A
Alt Allele: T
Freq: 41.5335%
CADD: 5.897
ClinVar Submissions (1)
Last Evaluated: Jul 05, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:30726777
Last Evaluated: Jul 05, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:30726777
Expert Reviewed drug response
Hetero
Gene:
CYP2C9
Variant:
CYP2C9*8
rsID: rs7900194
Ref Allele: G
Freq: 1.4776%uncommon
CADD: 7.328
ClinVar Submissions (1)
Last Evaluated: Feb 04, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96702066
Expert Reviewed drug response
Normal
Gene:
TCF7L2
Variant:
c.382-41435C>T
rsID: rs7903146
Ref Allele: C
Alt Allele: T
Freq: 22.7835%
CADD: 3.302
ClinVar Submissions (2)
Type 2 diabetes is a disorder characterized by abnormally high blood sugar levels. In this form of diabetes, the body stops using and making insulin properly. Insulin is a hormone produced in the pancreas that helps regulate blood sugar levels. Specifically, insulin controls how much glucose (a type of sugar) is passed from the blood into cells, where it is used as an energy source. When blood sugar levels are high (such as after a meal), the pancreas releases insulin to move the excess glucose into cells, which reduces the amount of glucose in the blood.Most people who develop type 2 diabetes first have insulin resistance, a condition in which the body's cells use insulin less efficiently than normal. As insulin resistance develops, more and more insulin is needed to keep blood sugar levels in the normal range. To keep up with the increasing need, insulin-producing cells in the pancreas (called beta cells) make larger amounts of insulin. Over time, the beta cells become less able to respond to blood sugar changes, leading to an insulin shortage that prevents the body from reducing blood sugar levels effectively. Most people have some insulin resistance as they age, but inadequate exercise and excessive weight gain make it worse, greatly increasing the likelihood of developing type 2 diabetes.Type 2 diabetes can occur at any age, but it most commonly begins in middle age or later. Signs and symptoms develop slowly over years. They include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, tingling or loss of feeling in the hands and feet (diabetic neuropathy), sores that do not heal well, and weight loss. If blood sugar levels are not controlled through medication or diet, type 2 diabetes can cause long-lasting (chronic) health problems including heart disease and stroke; nerve damage; and damage to the kidneys, eyes, and other parts of the body.
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:114758349
OMIM Allelic Variant: 602228.0001
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:114758349
OMIM Allelic Variant: 602228.0001
Insufficiently evaluated pathogenic — associated with colorectal cancer for the T allele.
Expert Reviewed drug response
Normal
Gene:
HTR2A
Variant:
c.614-2211T>C
rsID: rs7997012
Ref Allele: A
Alt Allele: G
Freq: 27.2764%
CADD: 9.414
ClinVar Submissions (3)
Last Evaluated: Mar 09, 2018
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 13:47411985
OMIM Allelic Variant: 182135.0003
Last Evaluated: Mar 09, 2018
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 13:47411985
OMIM Allelic Variant: 182135.0003
Last Evaluated: Mar 09, 2018
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 13:47411985
OMIM Allelic Variant: 182135.0003
Last Evaluated: Mar 09, 2018
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 13:47411985
OMIM Allelic Variant: 182135.0003
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Mar 09, 2018
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 13:47411985
OMIM Allelic Variant: 182135.0003
Expert Reviewed drug response
Normal
Gene:
IFNL3
Variant:
g.39252525T>G
rsID: rs8099917
Ref Allele: T
Alt Allele: G
Freq: 13.119%
CADD: 11.65
ClinVar Submissions (1)
Last Evaluated: Oct 16, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:39743165
Last Evaluated: Oct 16, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:39743165
Expert Reviewed drug response
Hetero
Gene:
VKORC1
Variant:
c.174-136C>T
rsID: rs9934438
Ref Allele: G
Alt Allele: A
Freq: 35.5831%
CADD: 11.64
ClinVar Submissions (5)
Last Evaluated: Apr 05, 2018
Review Status: reviewed by expert panel
Number of Submitters: 5
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:31104878
OMIM Allelic Variant: 608547.0008
Warfarin is an oral anti-coagulant used world-wide to treat and prevent thrombotic disorders. While it is highly effective, it has a very narrow therapeutic index making it difficult to dose correctly. Genetic variants in both cytochrome P450-2C9 (CYP2C9) and vitamin K-epoxide reductase complex (VKORC1) enzymes, along with non-genetic factors, are known to affect warfarin dose variability. Patients with specific variants in the gene CYP2C9 (the primary warfarin-metabolizing enzyme), such as CYP2C9*2 and CYP2C9*3, may require a lower dose of warfarin as compared to patients without these variants. Patients with a specific variant in VKORC1 (the target enzyme of warfarin), known as -1639G>A or rs9923231, may require a lower warfarin dose as compared to patients who do not have this variant. The combination of CYP2C9 and VKORC1 genetic variants, along with clinical factors, can put some patients at risk for adverse events such as bleeding. Guidelines regarding the use of pharmacogenomic tests in dosing for warfarin have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website.
Last Evaluated: Apr 05, 2018
Review Status: reviewed by expert panel
Number of Submitters: 5
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:31104878
OMIM Allelic Variant: 608547.0008
Last Evaluated: Apr 05, 2018
Review Status: reviewed by expert panel
Number of Submitters: 5
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:31104878
OMIM Allelic Variant: 608547.0008
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Apr 05, 2018
Review Status: reviewed by expert panel
Number of Submitters: 5
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:31104878
OMIM Allelic Variant: 608547.0008
Last Evaluated: Apr 05, 2018
Review Status: reviewed by expert panel
Number of Submitters: 5
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:31104878
OMIM Allelic Variant: 608547.0008
Last Evaluated: Apr 05, 2018
Review Status: reviewed by expert panel
Number of Submitters: 5
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:31104878
OMIM Allelic Variant: 608547.0008
Insufficiently evaluated pharmacogenetic — gene VKORC1 SNP 1173 C>T is strongly associated with low warfarin dose requirement.
Expert Reviewed drug response
Homo
Gene:
PTGS1
Variant:
c.-842A>G
rsID: rs10306114
Ref Allele: A
Alt Allele: G
Freq: 5.4113%
CADD: 4.793
ClinVar Submissions (1)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 9:125132522
Expert Reviewed drug response
Hetero
Gene:
LPA
Variant:
c.3947+467T>C
rsID: rs10455872
Ref Allele: A
Alt Allele: G
Freq: 2.2165%uncommon
CADD: 0.146
ClinVar Submissions (1)
Last Evaluated: May 08, 2018
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 6:161010118
Expert Reviewed drug response
Normal
Gene:
TANC1
Variant:
c.-125-6169A>C
rsID: rs10497203
Ref Allele: A
Alt Allele: C
Freq: 9.4449%
CADD: 1.974
ClinVar Submissions (1)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 2:159851423
Expert Reviewed drug response
Normal
Gene:
SLCO1B1
Variant:
c.1865+4846T>C
rsID: rs11045879
Ref Allele: T
Alt Allele: C
Freq: 21.9249%
CADD: 4.264
ClinVar Submissions (1)
Last Evaluated: Dec 20, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 12:21382619
Expert Reviewed drug response
Normal
Gene:
C11orf65
Variant:
c.175-5285G>T
rsID: rs11212617
Ref Allele: C
Alt Allele: A
Freq: 46.845%
CADD: 1.807
ClinVar Submissions (1)
Last Evaluated: Nov 17, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 11:108283161
Expert Reviewed drug response
Hetero
Gene:
NT5C2
Variant:
c.175+1178A>G
rsID: rs11598702
Ref Allele: T
Alt Allele: C
Freq: 25.5591%
CADD: 3.47
ClinVar Submissions (1)
Last Evaluated: Mar 19, 2015
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:104897985
Expert Reviewed drug response
Normal
Gene:
IFNL3
Variant:
c.259-126T>C
rsID: rs11881222
Ref Allele: A
Alt Allele: G
Freq: 25.1198%
CADD: 3.537
ClinVar Submissions (1)
Last Evaluated: Jun 14, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:39734923
Last Evaluated: Jun 14, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:39734923
Last Evaluated: Jun 14, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:39734923
Expert Reviewed drug response
Hetero
Gene:
CFTR
Variant:
c.3808G>A
(p.Asp1270Asn)
rsID: rs11971167
Ref Allele: G
Alt Allele: A
Freq: 0.5192%rare
CADD: 31
ClinVar Submissions (9)
Cystic fibrosis (CF) is a multisystem disease affecting epithelia of the respiratory tract, exocrine pancreas, intestine, hepatobiliary system, and exocrine sweat glands. Morbidities include progressive obstructive lung disease with bronchiectasis, frequent hospitalizations for pulmonary disease, pancreatic insufficiency and malnutrition, recurrent sinusitis and bronchitis, and male infertility. Pulmonary disease is the major cause of morbidity and mortality in CF. Meconium ileus occurs at birth in 15%-20% of newborns with CF. More than 95% of males with CF are infertile. Congenital absence of the vas deferens (CAVD) is generally identified during evaluation of infertility or as an incidental finding at the time of a surgical procedure. Hypoplasia or aplasia of the vas deferens and seminal vesicles may occur either bilaterally or unilaterally. Testicular development and function and spermatogenesis are usually normal.
Last Evaluated: May 15, 2018
Review Status: reviewed by expert panel
Number of Submitters: 9
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:117282582
OMIM Allelic Variant: 602421.0060
Cystic fibrosis (CF) is a multisystem disease affecting epithelia of the respiratory tract, exocrine pancreas, intestine, hepatobiliary system, and exocrine sweat glands. Morbidities include progressive obstructive lung disease with bronchiectasis, frequent hospitalizations for pulmonary disease, pancreatic insufficiency and malnutrition, recurrent sinusitis and bronchitis, and male infertility. Pulmonary disease is the major cause of morbidity and mortality in CF. Meconium ileus occurs at birth in 15%-20% of newborns with CF. More than 95% of males with CF are infertile. Congenital absence of the vas deferens (CAVD) is generally identified during evaluation of infertility or as an incidental finding at the time of a surgical procedure. Hypoplasia or aplasia of the vas deferens and seminal vesicles may occur either bilaterally or unilaterally. Testicular development and function and spermatogenesis are usually normal.
Last Evaluated: May 15, 2018
Review Status: reviewed by expert panel
Number of Submitters: 9
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:117282582
OMIM Allelic Variant: 602421.0060
A disorder characterized by recurrent episodes of pancreatitis that start at a young age. It is caused by mutations in the PRSS1 or SPINK1 genes. Patients are at a high risk of developing pancreatic carcinoma.
Last Evaluated: May 15, 2018
Review Status: reviewed by expert panel
Number of Submitters: 9
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:117282582
OMIM Allelic Variant: 602421.0060
Last Evaluated: May 15, 2018
Review Status: reviewed by expert panel
Number of Submitters: 9
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:117282582
OMIM Allelic Variant: 602421.0060
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: May 15, 2018
Review Status: reviewed by expert panel
Number of Submitters: 9
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:117282582
OMIM Allelic Variant: 602421.0060
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: May 15, 2018
Review Status: reviewed by expert panel
Number of Submitters: 9
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:117282582
OMIM Allelic Variant: 602421.0060
This individual has one copy of the genetic mutation, and depending on the condition, this mutation can act as either autosomal dominant or recessive. Thus, they might manifest one condition while being a carrier for another. However, it's important to conduct thorough research before drawing definitive conclusions.
Expert Reviewed Clinically Significant drug response
Normal
Gene:
CYP2C19
Variant:
c.-806C>A
rsID: rs12248560
Ref Allele: C
Alt Allele: A
Freq: 15.3155%
CADD: 0.421
ClinVar Submissions (1)
Last Evaluated: Aug 17, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96521657
Last Evaluated: Aug 17, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96521657
Last Evaluated: Aug 17, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96521657
Expert Reviewed drug response
Normal
Gene:
-
Variant:
g.94645745G>A
rsID: rs12777823
Ref Allele: G
Alt Allele: A
Freq: 24.5407%
CADD: 0.86
ClinVar Submissions (1)
Last Evaluated: Mar 09, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96405502
Expert Reviewed drug response
Homo
Gene:
IFNL3;IFNL4
Variant:
c.151-152G>A
rsID: rs12979860
Ref Allele: C
Alt Allele: T
Freq: 35.5831%
CADD: 6.01
ClinVar Submissions (2)
Last Evaluated: Apr 05, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:39738787
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Apr 05, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:39738787
Last Evaluated: Apr 05, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:39738787
Last Evaluated: Apr 05, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:39738787
Last Evaluated: Apr 05, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:39738787
Last Evaluated: Apr 05, 2018
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:39738787
Expert Reviewed drug response
Hetero
Gene:
COMT;TXNRD2
Variant:
c.103+197G>A
rsID: rs13306278
Ref Allele: C
Alt Allele: T
Freq: 7.7276%
CADD: 12.06
ClinVar Submissions (1)
Last Evaluated: Jun 22, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 22:19929027
Expert Reviewed drug response
Hetero
Gene:
PRKCA
Variant:
c.1854+3730G>A
rsID: rs16960228
Ref Allele: G
Alt Allele: A
Freq: 15.7348%
CADD: 0.133
ClinVar Submissions (1)
Last Evaluated: Jul 11, 2016
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 17:64788827
Expert Reviewed drug response
Normal
Gene:
HMGCR
Variant:
c.451-174A>T
rsID: rs17244841
Ref Allele: A
Alt Allele: T
Freq: 3.6941%uncommon
CADD: 0.045
ClinVar Submissions (2)
Last Evaluated: Oct 14, 2015
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 5:74642855
OMIM Allelic Variant: 142910.0001
Last Evaluated: Oct 14, 2015
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 5:74642855
OMIM Allelic Variant: 142910.0001
Last Evaluated: Oct 14, 2015
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 5:74642855
OMIM Allelic Variant: 142910.0001
Last Evaluated: Oct 14, 2015
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 5:74642855
OMIM Allelic Variant: 142910.0001
Expert Reviewed drug response
Normal
Gene:
VKORC1
Variant:
c.173+525C>T
rsID: rs17708472
Ref Allele: G
Alt Allele: A
Freq: 9.365%
CADD: 8.333
ClinVar Submissions (1)
Last Evaluated: Oct 29, 2014
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:31105353
Expert Reviewed drug response
Normal
Gene:
MC4R
Variant:
g.60183864T>C
rsID: rs17782313
Ref Allele: T
Alt Allele: C
Freq: 24.0016%
CADD: 3.755
ClinVar Submissions (1)
Last Evaluated: Sep 22, 2015
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 18:57851097
Expert Reviewed drug response
Normal
Gene:
CYP2C9
Variant:
c.1080C>G
(p.Asp360Glu)
rsID: rs28371686
Ref Allele: C
Alt Allele: G
Freq: 0.4593%rare
CADD: 16.55
ClinVar Submissions (2)
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Nov 06, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96741058
Last Evaluated: Nov 06, 2017
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96741058
Expert Reviewed drug response
Normal
Gene:
CYP2B6
Variant:
c.983T>C
(p.Ile328Thr)
rsID: rs28399499
Ref Allele: T
Alt Allele: C
Freq: 2.3163%uncommon
CADD: 24.6
ClinVar Submissions (1)
Last Evaluated: Dec 05, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:41518221
Last Evaluated: Dec 05, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:41518221
Last Evaluated: Dec 05, 2017
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 19:41518221
Insufficiently evaluated pharmacogenetic — Elevated plasma levels of efavirenz. Also associated with response to bupropion and nevirapine.
Expert Reviewed drug response
Normal
Gene:
CYP2C19
Variant:
c.1A>G
(p.Met1Val)
rsID: rs28399504
Ref Allele: A
Alt Allele: G
Freq: 0.0799%rare
CADD: 14.54
ClinVar Submissions (3)
Last Evaluated: Dec 28, 2015
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96522463
OMIM Allelic Variant: 124020.0004
Last Evaluated: Dec 28, 2015
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96522463
OMIM Allelic Variant: 124020.0004
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Dec 28, 2015
Review Status: reviewed by expert panel
Number of Submitters: 3
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 10:96522463
OMIM Allelic Variant: 124020.0004
Insufficiently evaluated pathogenic — This variant creates the CYP2C19*4 haplotype which is associated with poor metabolism of mephenytoin.
Expert Reviewed drug response
Normal
Gene:
DPYD
Variant:
c.1679T>G
(p.Ile560Ser)
rsID: rs55886062
Ref Allele: A
Alt Allele: C
Freq: 0.02%rare
CADD: 28.7
ClinVar Submissions (4)
Last Evaluated: Jan 11, 2018
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97981343
Last Evaluated: Jan 11, 2018
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97981343
Last Evaluated: Jan 11, 2018
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97981343
Last Evaluated: Jan 11, 2018
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97981343
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Jan 11, 2018
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97981343
Last Evaluated: Jan 11, 2018
Review Status: reviewed by expert panel
Number of Submitters: 4
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97981343
The data does not specify whether the genetic variant is autosomal recessive or autosomal dominant. For a definitive determination, refer to resources such as OMIM.
Expert Reviewed Clinically Significant drug response
Normal
Gene:
DPYD
Variant:
c.2846A>T
(p.Asp949Val)
rsID: rs67376798
Ref Allele: T
Alt Allele: A
Freq: 0.2196%rare
CADD: 25.2
ClinVar Submissions (6)
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 6
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97547947
5-fluorouracil is a chemotherapeutic agent, and a member of the fluoropyrimidine group of substances. It is mainly used to treat solid tumors, such as colorectal, breast and aerodigestive cancers. Dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene) is the rate-limiting enzyme for fluoropyrimidine metabolism and is therefore responsible for the detoxification of these types of drugs. Patients who are homozygous for variants in DPYD that lead to a non-functional protein, such as *2A or *13, have a high risk of severe or fatal drug toxicities and may benefit from receiving an alternative chemotherapeutic drug. Patients heterozygous for these variants also have an increased risk for drug toxicities, and reduced dosing is recommended for these individuals. Guidelines regarding the use of pharmacogenomic tests in dosing for 5-fluorouracil have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website (http://www.pharmgkb.org/drug/PA128406956).
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 6
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97547947
Diseases that are caused by genetic mutations present during embryo or fetal development, although they may be observed later in life. The mutations may be inherited from a parent's genome or they may be acquired in utero.
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 6
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97547947
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 6
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97547947
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 6
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97547947
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 6
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97547947
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 6
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97547947
Last Evaluated: May 14, 2018
Review Status: reviewed by expert panel
Number of Submitters: 6
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 1:97547947
The data does not specify whether the genetic variant is autosomal recessive or autosomal dominant. For a definitive determination, refer to resources such as OMIM.
Expert Reviewed Clinically Significant drug response
Normal
Gene:
CES1
Variant:
c.431G>A
(p.Gly144Glu)
rsID: rs71647871
Ref Allele: C
Alt Allele: T
CADD: 21.2
ClinVar Submissions (1)
Last Evaluated: Oct 28, 2015
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 16:55857570
Expert Reviewed drug response
Normal
Gene:
CFTR
Variant:
c.349C>A
(p.Arg117Ser)
rsID: rs77834169
Ref Allele: C
Alt Allele: A
CADD: 24.7
ClinVar Submissions (1)
Last Evaluated: Mar 22, 2018
Review Status: reviewed by expert panel
Number of Submitters: 1
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 7:117171028
Expert Reviewed drug response
Normal
Gene:
NUDT15
Variant:
c.415C>T
(p.Arg139Cys)
rsID: rs116855232
Ref Allele: C
Alt Allele: T
Freq: 3.9537%uncommon
CADD: 17.44
ClinVar Submissions (2)
THPM2 is associated with severe hematopoietic toxicity when patients are treated with standard doses of thiopurines, a class of antineoplastic/immunosuppressant agents that consists of mercaptopurine, thioguanine, and azathioprine. Thiopurines are prodrugs that require extensive metabolism in order to exert their cytotoxic action. Thiopurines are converted into cytotoxic thioguanine nucleotides (TG), which are incorporated into DNA and cause cell death. NUDT15 inactivates thiopurine metabolites and negatively regulates cytotoxicity (summary by Moriyama et al., 2016). The NUDT15 deficiency trait follows an additive genetic mode of inheritance, with the severity of the phenotype proportional to the cumulative number of risk alleles in NUDT15. For a discussion of genetic heterogeneity of poor thiopurine metabolism, see THPM1 (610460).
Last Evaluated: Mar 22, 2019
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 13:48619855
OMIM Allelic Variant: 615792.0001
Last Evaluated: Mar 22, 2019
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 13:48619855
OMIM Allelic Variant: 615792.0001
Last Evaluated: Mar 22, 2019
Review Status: reviewed by expert panel
Number of Submitters: 2
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: 13:48619855
OMIM Allelic Variant: 615792.0001
Expert Reviewed drug response
Normal
Gene:
CFTR
Variant:
c.1647T>G
(p.Ser549Arg)
rsID: rs121909005
Ref Allele: T
Alt Allele: G
CADD: 24.7
ClinVar Submissions (7)
Cystic fibrosis (CF) is a multisystem disease affecting epithelia of the respiratory tract, exocrine pancreas, intestine, hepatobiliary system, and exocrine sweat glands. Morbidities include progressive obstructive lung disease with bronchiectasis, frequent hospitalizations for pulmonary disease, pancreatic insufficiency and malnutrition, recurrent sinusitis and bronchitis, and male infertility. Pulmonary disease is the major cause of morbidity and mortality in CF. Meconium ileus occurs at birth in 15%-20% of newborns with CF. More than 95% of males with CF are infertile. Congenital absence of the vas deferens (CAVD) is generally identified during evaluation of infertility or as an incidental finding at the time of a surgical procedure. Hypoplasia or aplasia of the vas deferens and seminal vesicles may occur either bilaterally or unilaterally. Testicular development and function and spermatogenesis are usually normal.
Last Evaluated: Nov 05, 2018
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: Pathogenic, drug response
Assembly: GRCh37
Chromosome/Position: 7:117227855
OMIM Allelic Variant: 602421.0012
Last Evaluated: Nov 05, 2018
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: Pathogenic, drug response
Assembly: GRCh37
Chromosome/Position: 7:117227855
OMIM Allelic Variant: 602421.0012
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Nov 05, 2018
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: Pathogenic, drug response
Assembly: GRCh37
Chromosome/Position: 7:117227855
OMIM Allelic Variant: 602421.0012
This individual has one copy of the genetic mutation, and because it's autosomal recessive, they are likely a carrier rather than manifesting the condition. Interpretation of carrier status should be backed by thorough research.
Expert Reviewed Clinically Significant Pathogenic, drug response
Normal
Gene:
MT-CO1;MT-RNR1
Variant:
m.1555A>G
rsID: rs267606617
Ref Allele: A
Alt Allele: G
ClinVar Submissions (7)
Last Evaluated: Aug 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: MT:1555
OMIM Allelic Variant: 561000.0001
Last Evaluated: Aug 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: MT:1555
OMIM Allelic Variant: 561000.0001
Last Evaluated: Aug 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: MT:1555
OMIM Allelic Variant: 561000.0001
Last Evaluated: Aug 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: MT:1555
OMIM Allelic Variant: 561000.0001
Last Evaluated: Aug 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: MT:1555
OMIM Allelic Variant: 561000.0001
Last Evaluated: Aug 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: MT:1555
OMIM Allelic Variant: 561000.0001
Last Evaluated: Aug 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: MT:1555
OMIM Allelic Variant: 561000.0001
Last Evaluated: Aug 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: MT:1555
OMIM Allelic Variant: 561000.0001
Last Evaluated: Aug 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: MT:1555
OMIM Allelic Variant: 561000.0001
Last Evaluated: Aug 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: MT:1555
OMIM Allelic Variant: 561000.0001
Last Evaluated: Aug 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: MT:1555
OMIM Allelic Variant: 561000.0001
Last Evaluated: Aug 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: MT:1555
OMIM Allelic Variant: 561000.0001
Last Evaluated: Aug 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: MT:1555
OMIM Allelic Variant: 561000.0001
Last Evaluated: Aug 01, 2018
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: drug response
Assembly: GRCh37
Chromosome/Position: MT:1555
OMIM Allelic Variant: 561000.0001
The data does not specify whether the genetic variant is autosomal recessive or autosomal dominant. For a definitive determination, refer to resources such as OMIM.
Expert Reviewed Clinically Significant drug response
Normal
Below are mutations from ClinVar that were submitted as "clinically significant." Variants shown may or may not be truly clinically significant. The data presented has no guarantees of reporting accuracy. Heterozygous variants are reported as yellow and homozygous variants as red. A red or yellow variant does not necessarily mean one has or carries a condition or disease. This is for research and educational purposes only.
Gene:
RAPSN
Variant:
c.264C>A
(p.Asn88Lys)
rsID: rs104894299
Ref Allele: G
Alt Allele: T
Freq: 0.1198%rare
CADD: 26.6
ClinVar Submissions (13)
Last Evaluated: Jun 19, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 13
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:47469631
OMIM Allelic Variant: 601592.0001
Congenital myasthenic syndromes (designated as CMS throughout this entry) are characterized by fatigable weakness of skeletal muscle (e.g., ocular, bulbar, limb muscles) with onset at or shortly after birth or in early childhood; rarely, symptoms may not manifest until later in childhood. Cardiac and smooth muscle are usually not involved. Severity and course of disease are highly variable, ranging from minor symptoms to progressive disabling weakness. In some subtypes of CMS, myasthenic symptoms may be mild, but sudden severe exacerbations of weakness or even sudden episodes of respiratory insufficiency may be precipitated by fever, infections, or excitement. Major findings of the neonatal-onset subtype include: respiratory insufficiency with sudden apnea and cyanosis; feeding difficulties; poor suck and cry; choking spells; eyelid ptosis; and facial, bulbar, and generalized weakness. Arthrogryposis multiplex congenita may also be present. Stridor in infancy may be an important clue to CMS. Later childhood-onset subtypes show abnormal muscle fatigability with difficulty in activities such as running or climbing stairs; motor milestones may be delayed; fluctuating eyelid ptosis and fixed or fluctuating extraocular muscle weakness are common presentations.
Last Evaluated: Jun 19, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 13
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:47469631
OMIM Allelic Variant: 601592.0001
A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.
Last Evaluated: Jun 19, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 13
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:47469631
OMIM Allelic Variant: 601592.0001
Congenital myasthenic syndromes (designated as CMS throughout this entry) are characterized by fatigable weakness of skeletal muscle (e.g., ocular, bulbar, limb muscles) with onset at or shortly after birth or in early childhood; rarely, symptoms may not manifest until later in childhood. Cardiac and smooth muscle are usually not involved. Severity and course of disease are highly variable, ranging from minor symptoms to progressive disabling weakness. In some subtypes of CMS, myasthenic symptoms may be mild, but sudden severe exacerbations of weakness or even sudden episodes of respiratory insufficiency may be precipitated by fever, infections, or excitement. Major findings of the neonatal-onset subtype include: respiratory insufficiency with sudden apnea and cyanosis; feeding difficulties; poor suck and cry; choking spells; eyelid ptosis; and facial, bulbar, and generalized weakness. Arthrogryposis multiplex congenita may also be present. Stridor in infancy may be an important clue to CMS. Later childhood-onset subtypes show abnormal muscle fatigability with difficulty in activities such as running or climbing stairs; motor milestones may be delayed; fluctuating eyelid ptosis and fixed or fluctuating extraocular muscle weakness are common presentations.
Last Evaluated: Jun 19, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 13
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:47469631
OMIM Allelic Variant: 601592.0001
Congenital myasthenic syndromes (designated as CMS throughout this entry) are characterized by fatigable weakness of skeletal muscle (e.g., ocular, bulbar, limb muscles) with onset at or shortly after birth or in early childhood; rarely, symptoms may not manifest until later in childhood. Cardiac and smooth muscle are usually not involved. Severity and course of disease are highly variable, ranging from minor symptoms to progressive disabling weakness. In some subtypes of CMS, myasthenic symptoms may be mild, but sudden severe exacerbations of weakness or even sudden episodes of respiratory insufficiency may be precipitated by fever, infections, or excitement. Major findings of the neonatal-onset subtype include: respiratory insufficiency with sudden apnea and cyanosis; feeding difficulties; poor suck and cry; choking spells; eyelid ptosis; and facial, bulbar, and generalized weakness. Arthrogryposis multiplex congenita may also be present. Stridor in infancy may be an important clue to CMS. Later childhood-onset subtypes show abnormal muscle fatigability with difficulty in activities such as running or climbing stairs; motor milestones may be delayed; fluctuating eyelid ptosis and fixed or fluctuating extraocular muscle weakness are common presentations.
Last Evaluated: Jun 19, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 13
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:47469631
OMIM Allelic Variant: 601592.0001
Congenital myasthenic syndromes (designated as CMS throughout this entry) are characterized by fatigable weakness of skeletal muscle (e.g., ocular, bulbar, limb muscles) with onset at or shortly after birth or in early childhood; rarely, symptoms may not manifest until later in childhood. Cardiac and smooth muscle are usually not involved. Severity and course of disease are highly variable, ranging from minor symptoms to progressive disabling weakness. In some subtypes of CMS, myasthenic symptoms may be mild, but sudden severe exacerbations of weakness or even sudden episodes of respiratory insufficiency may be precipitated by fever, infections, or excitement. Major findings of the neonatal-onset subtype include: respiratory insufficiency with sudden apnea and cyanosis; feeding difficulties; poor suck and cry; choking spells; eyelid ptosis; and facial, bulbar, and generalized weakness. Arthrogryposis multiplex congenita may also be present. Stridor in infancy may be an important clue to CMS. Later childhood-onset subtypes show abnormal muscle fatigability with difficulty in activities such as running or climbing stairs; motor milestones may be delayed; fluctuating eyelid ptosis and fixed or fluctuating extraocular muscle weakness are common presentations.
Last Evaluated: Jun 19, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 13
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:47469631
OMIM Allelic Variant: 601592.0001
The fetal akinesia deformation sequence (FADS) refers to a clinically and genetically heterogeneous constellation of features including fetal akinesia, intrauterine growth retardation, arthrogryposis, and developmental anomalies, including lung hypoplasia, cleft palate, and cryptorchidism (Vogt et al., 2009). It shows phenotypic overlap with the lethal form of multiple pterygium syndrome (see 253290).
Last Evaluated: Jun 19, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 13
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:47469631
OMIM Allelic Variant: 601592.0001
The fetal akinesia deformation sequence (FADS) refers to a clinically and genetically heterogeneous constellation of features including fetal akinesia, intrauterine growth retardation, arthrogryposis, and developmental anomalies, including lung hypoplasia, cleft palate, and cryptorchidism (Vogt et al., 2009). It shows phenotypic overlap with the lethal form of multiple pterygium syndrome (see 253290).
Last Evaluated: Jun 19, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 13
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:47469631
OMIM Allelic Variant: 601592.0001
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Jun 19, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 13
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:47469631
OMIM Allelic Variant: 601592.0001
This individual has one copy of the genetic mutation, and because it's autosomal recessive, they are likely a carrier rather than manifesting the condition. This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
High clinical importance, Likely pathogenic — Causes congenital myasthenic syndrome in a recessive manner (when homozygous or combined with another deleterious variant in the same gene).
Clinically Significant Conflicting/Uncertain
Hetero
Gene:
LAMA2
Variant:
c.4487C>T
(p.Ala1496Val)
rsID: rs147077184
Ref Allele: C
Alt Allele: T
Freq: 0.2796%rare
CADD: 24
ClinVar Submissions (10)
The clinical manifestations of LAMA2-related muscular dystrophy (LAMA2 MD) range from severe, early-onset congenital muscular dystrophy (CMD) – referred to as early-onset LAMA2-related muscular dystrophy (LAMA2 MD) in this GeneReview – to mild, later childhood-onset limb-girdle type muscular dystrophy – referred to here as late-onset LAMA2-related muscular dystrophy (LAMA2 MD). Children with early-onset LAMA2 MD have profound hypotonia with muscle weakness evident at birth or within the first six months of life, poor spontaneous movements with contractures of the large joints, and weak cry often associated with respiratory failure. Feeding difficulties with failure to thrive, aspiration, and recurrent chest infections are typical. Progressive scoliosis starting in childhood is common. Seizures and, less often, cardiac involvement can occur. Typically, individuals with early-onset LAMA2 MD do not achieve independent ambulation. Intellect is usually normal. Those with limb-girdle type muscular dystrophy have later onset of proximal muscle weakness and delayed motor milestones, but achieve independent ambulation; they may develop a rigid spine syndrome with joint contractures. Progressive respiratory insufficiency and scoliosis can occur.
Last Evaluated: Oct 05, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 10
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 6:129670493
OMIM Allelic Variant: 156225.0019
The clinical manifestations of LAMA2-related muscular dystrophy (LAMA2 MD) range from severe, early-onset congenital muscular dystrophy (CMD) – referred to as early-onset LAMA2-related muscular dystrophy (LAMA2 MD) in this GeneReview – to mild, later childhood-onset limb-girdle type muscular dystrophy – referred to here as late-onset LAMA2-related muscular dystrophy (LAMA2 MD). Children with early-onset LAMA2 MD have profound hypotonia with muscle weakness evident at birth or within the first six months of life, poor spontaneous movements with contractures of the large joints, and weak cry often associated with respiratory failure. Feeding difficulties with failure to thrive, aspiration, and recurrent chest infections are typical. Progressive scoliosis starting in childhood is common. Seizures and, less often, cardiac involvement can occur. Typically, individuals with early-onset LAMA2 MD do not achieve independent ambulation. Intellect is usually normal. Those with limb-girdle type muscular dystrophy have later onset of proximal muscle weakness and delayed motor milestones, but achieve independent ambulation; they may develop a rigid spine syndrome with joint contractures. Progressive respiratory insufficiency and scoliosis can occur.
Last Evaluated: Oct 05, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 10
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 6:129670493
OMIM Allelic Variant: 156225.0019
Merosin-deficient congenital muscular dystrophy is an autosomal recessive form of muscular dystrophy characterized by muscle weakness apparent at birth or in the first 6 months of life. Patients show hypotonia, poor suck and cry, and delayed motor development; most never achieve independent ambulation. Most patients also have periventricular white matter abnormalities on brain imaging, but mental retardation and/or seizures occur only rarely (summary by Xiong et al., 2015).
Last Evaluated: Oct 05, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 10
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 6:129670493
OMIM Allelic Variant: 156225.0019
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Oct 05, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 10
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 6:129670493
OMIM Allelic Variant: 156225.0019
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Oct 05, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 10
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 6:129670493
OMIM Allelic Variant: 156225.0019
This individual has one copy of the genetic mutation, and because it's autosomal recessive, they are likely a carrier rather than manifesting the condition. This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Clinically Significant Conflicting/Uncertain
Hetero
Gene:
BLK
Variant:
c.211G>A
(p.Ala71Thr)
rsID: rs55758736
Ref Allele: G
Alt Allele: A
Freq: 1.238%uncommon
CADD: 13.44
ClinVar Submissions (7)
Maturity-onset diabetes of the young is an autosomal dominant form of diabetes typically occurring before 25 years of age and caused by primary insulin secretion defects. Despite its low prevalence, MODY is not a single entity but represents genetic, metabolic, and clinical heterogeneity (Vaxillaire and Froguel, 2008). Genetic Heterogeneity of MODY MODY1 (125850) is caused by heterozygous mutation in the hepatocyte nuclear factor-4-alpha gene (HNF4A; 600281) on chromosome 20. MODY2 (125851) is caused by heterozygous mutation in the glucokinase gene (GCK; 138079) on chromosome 7. MODY3 (600496) is caused by heterozygous mutation in the hepatocyte nuclear factor-1alpha gene (HNF1A; 142410) on chromosome 12q24.2. MODY4 (606392) is caused by heterozygous mutation in the pancreas/duodenum homeobox protein-1 gene (PDX1; 600733) on chromosome 13q12.1. MODY5 (137920) is caused by heterozygous mutation in the gene encoding hepatic transcription factor-2 (TCF2; 189907) on chromosome 17cen-q21.3. MODY6 (606394) is caused by heterozygous mutation in the NEUROD1 gene (601724) on chromosome 2q32. MODY7 (610508) is caused by heterozygous mutation in the KLF11 gene (603301) on chromosome 2p25. MODY8 (609812), or diabetes-pancreatic exocrine dysfunction syndrome, is caused by heterozygous mutation in the CEL gene (114840) on chromosome 9q34. MODY9 (612225) is caused by heterozygous mutation in the PAX4 gene (167413) on chromosome 7q32. MODY10 (613370) is caused by heterozygous mutation in the insulin gene (INS; 176730) on chromosome 11p15.5. MODY11 (613375) is caused by heterozygous mutation in the BLK gene (191305) on chromosome 8p23. MODY13 (616329) is caused by heterozygous mutation in the KCNJ11 gene (600937) on chromosome 11p15. MODY14 (616511) is caused by heterozygous mutation in the APPL1 gene (604299) on chromosome 3p14.
Last Evaluated: Apr 21, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 7
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 8:11405576
OMIM Allelic Variant: 191305.0001
Last Evaluated: Apr 21, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 7
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 8:11405576
OMIM Allelic Variant: 191305.0001
Diabetes mellitus caused by mutation(s) in a single gene, usually presenting in childhood or early adulthood.
Last Evaluated: Apr 21, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 7
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 8:11405576
OMIM Allelic Variant: 191305.0001
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Apr 21, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 7
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 8:11405576
OMIM Allelic Variant: 191305.0001
This individual has one copy of the genetic mutation, and because the condition(s) are autosomal dominant, they may manifest the condition rather than just being a carrier. This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Clinically Significant Conflicting/Uncertain
Hetero
Gene:
SPTA1
Variant:
c.2909C>A
(p.Ala970Asp)
rsID: rs35948326
Ref Allele: G
Alt Allele: T
Freq: 1.4177%uncommon
CADD: 22.5
ClinVar Submissions (5)
Last Evaluated: Apr 13, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 5
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 1:158624528
OMIM Allelic Variant: 182860.0009
Last Evaluated: Apr 13, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 5
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 1:158624528
OMIM Allelic Variant: 182860.0009
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Apr 13, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 5
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 1:158624528
OMIM Allelic Variant: 182860.0009
The data does not specify whether the genetic variant is autosomal recessive or autosomal dominant. For a definitive determination, refer to resources such as OMIM. This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Low clinical importance, Uncertain benign — This variant, also called alpha-IIa, has been seen frequently in individuals with recessive Hereditary spherocytosis. This appears to be the result of linkage to alpha-LEPRA (a C>T substitution at position -99 of intron 30); A970D is later reported as functionally neutral.
Clinically Significant Conflicting/Uncertain
Hetero
Gene:
MC1R
Variant:
c.451C>T
(p.Arg151Cys)
rsID: rs1805007
Ref Allele: C
Alt Allele: T
Freq: 1.857%uncommon
CADD: 31
ClinVar Submissions (5)
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 5
Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
Assembly: GRCh37
Chromosome/Position: 16:89986117
OMIM Allelic Variant: 155555.0004
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 5
Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
Assembly: GRCh37
Chromosome/Position: 16:89986117
OMIM Allelic Variant: 155555.0004
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 5
Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
Assembly: GRCh37
Chromosome/Position: 16:89986117
OMIM Allelic Variant: 155555.0004
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 5
Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
Assembly: GRCh37
Chromosome/Position: 16:89986117
OMIM Allelic Variant: 155555.0004
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 5
Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
Assembly: GRCh37
Chromosome/Position: 16:89986117
OMIM Allelic Variant: 155555.0004
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 5
Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
Assembly: GRCh37
Chromosome/Position: 16:89986117
OMIM Allelic Variant: 155555.0004
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 5
Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
Assembly: GRCh37
Chromosome/Position: 16:89986117
OMIM Allelic Variant: 155555.0004
The data does not specify whether the genetic variant is autosomal recessive or autosomal dominant. For a definitive determination, refer to resources such as OMIM. This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Insufficiently evaluated benign — The MC1R gene encodes for a receptor protein for a melanin-stimulating hormone, so it is involved in melanogenesis (melanin production). Polymorphisms of this gene have been shown to cause increased susceptibility of skin cells to UV damage. Arg151Cys has been associated with melanoma.
Clinically Significant Conflicting/Uncertain
Hetero
Gene:
AMPD1
Variant:
c.133C>T
(p.Gln45Ter)
rsID: rs17602729
Ref Allele: G
Alt Allele: A
Freq: 3.8139%uncommon
CADD: 36
ClinVar Submissions (6)
Myoadenylate deaminase deficiency (MMDD) is an autosomal recessive condition that can manifest as exercise-induced muscle pain, occasionally associated with rhabdomyolysis and/or increased serum creatine kinase, or even infantile hypotonia. However, the finding of homozygous mutations among asymptomatic individuals have suggested to some (e.g., Verzijl et al., 1998) that AMPD1 deficiency may be a harmless entity (summary by Castro-Gago et al., 2011). Genetta et al. (2001) stated that AMPD1 deficiency is the most prevalent genetic disease in humans, the number of people heterozygous approaching 10% of Caucasians and individuals of African descent (Sabina et al., 1989). A small percentage of homozygous-deficient individuals, approximately 1.8% of the population, display symptoms of chronic fatigue and lost productivity as well as a predisposition to stress-related ailments, including heart disease and stroke, according to Genetta et al. (2001).
Last Evaluated: Jun 27, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 6
Clinical Significance: Conflicting interpretations of pathogenicity, other
Assembly: GRCh37
Chromosome/Position: 1:115236057
OMIM Allelic Variant: 102770.0001
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Jun 27, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 6
Clinical Significance: Conflicting interpretations of pathogenicity, other
Assembly: GRCh37
Chromosome/Position: 1:115236057
OMIM Allelic Variant: 102770.0001
The individual has two copies of the variant, which suggests they may manifest the associated condition or trait. This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Low clinical importance, Likely pathogenic — Causes Adenosine Deaminase Deficiency in a recessive manner. Most of the time individuals do not report symptoms, but when symptoms do exist they to be post-exercise symptoms of muscle weakness, muscle pain, and getting tired more quickly.
Expert Reviewed Clinically Significant Conflicting/Uncertain
Homo
Gene:
HPD
Variant:
c.97G>A
(p.Ala33Thr)
rsID: rs1154510
Ref Allele: C
Alt Allele: T
Freq: 12.3602%
ClinVar Submissions (2)
Hawkinsinuria is an autosomal dominant inborn error of metabolism (Danks et al., 1975; Tomoeda et al., 2000). Metabolic acidosis and tyrosinemia are transient, and symptoms improve within the first year of life. Patients continue to excrete the hawkinsin metabolite in their urine throughout life.
Last Evaluated: Nov 21, 2017
Review Status: criteria provided, single submitter
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 12:122295335
OMIM Allelic Variant: 609695.0005
Hawkinsinuria is an autosomal dominant inborn error of metabolism (Danks et al., 1975; Tomoeda et al., 2000). Metabolic acidosis and tyrosinemia are transient, and symptoms improve within the first year of life. Patients continue to excrete the hawkinsin metabolite in their urine throughout life.
Last Evaluated: Nov 21, 2017
Review Status: criteria provided, single submitter
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 12:122295335
OMIM Allelic Variant: 609695.0005
Tyrosinemia type III is an autosomal recessive disorder caused by a deficiency in the activity of 4-hydroxyphenylpyruvate dioxygenase (HPD) and is characterized by elevated levels of blood tyrosine and massive excretion of its derivatives into urine. Patients with this disorder have mild mental retardation and/or convulsions, with the absence of liver damage (summary by Tomoeda et al., 2000).
Last Evaluated: Nov 21, 2017
Review Status: criteria provided, single submitter
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 12:122295335
OMIM Allelic Variant: 609695.0005
This individual has one copy of the genetic mutation, and depending on the condition, this mutation can act as either autosomal dominant or recessive. Thus, they might manifest one condition while being a carrier for another. However, it's important to conduct thorough research before drawing definitive conclusions.
Clinically Significant Benign
Hetero
Gene:
DCAF17
Variant:
c.322-14C>T
rsID: rs192861143
Ref Allele: C
Alt Allele: T
Freq: 20.7069%
CADD: 0.483
ClinVar Submissions (3)
Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurologic disorders in which iron accumulates in the basal ganglia resulting in progressive dystonia, spasticity, parkinsonism, neuropsychiatric abnormalities, and optic atrophy or retinal degeneration. Ten types and their associated genes are recognized. The age of onset ranges from infancy to late adulthood; the rate of progression varies. Cognitive decline occurs in some subtypes, but more often cognition is relatively spared. Cerebellar atrophy is a frequent finding in some subtypes.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 2:172305177
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 2:172305177
This individual has one copy of the genetic mutation, and because it's autosomal recessive, they are likely a carrier rather than manifesting the condition. Interpretation of carrier status should be backed by thorough research.
Clinically Significant Benign
Hetero
Gene:
DPYD
Variant:
c.85T>C
(p.Cys29Arg)
rsID: rs1801265
Ref Allele: A
Alt Allele: G
Freq: 26.0184%
ClinVar Submissions (2)
Last Evaluated: Nov 20, 2017
Review Status: criteria provided, single submitter
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 1:98348885
OMIM Allelic Variant: 612779.0004
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Nov 20, 2017
Review Status: criteria provided, single submitter
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 1:98348885
OMIM Allelic Variant: 612779.0004
The data does not specify whether the genetic variant is autosomal recessive or autosomal dominant. For a definitive determination, refer to resources such as OMIM.
Insufficiently evaluated pharmacogenetic — This variant is also known as DPYD*9A, and is associated with Dihydropyrimidine dehydrogenase deficiency and impaired clearance of 5-fluorouracil with potential toxic consequence.
Clinically Significant Benign
Hetero
Gene:
FGFR4
Variant:
c.1162G>A
(p.Gly388Arg)
rsID: rs351855
Ref Allele: G
Alt Allele: A
Freq: 29.9521%
CADD: 24
ClinVar Submissions (1)
Last Evaluated: Feb 01, 2002
Review Status: no assertion criteria provided
Number of Submitters: 1
Clinical Significance: Pathogenic
Assembly: GRCh37
Chromosome/Position: 5:176520243
OMIM Allelic Variant: 134935.0001
The data does not specify whether the genetic variant is autosomal recessive or autosomal dominant. For a definitive determination, refer to resources such as OMIM.
Insufficiently evaluated pharmacogenetic — Possible association with sensitivity to cisplatin; poor outcome with cyclophosphamide, fluoruracil, methotextrate and tamoxifen.
Clinically Significant Pathogenic
Hetero
Gene:
CCL2
Variant:
g.2493A>G
rsID: rs1024611
Ref Allele: A
Alt Allele: G
Freq: 36.3618%
CADD: 3.685
ClinVar Submissions (1)
Last Evaluated: Jan 15, 2009
Review Status: no assertion criteria provided
Number of Submitters: 1
Clinical Significance: Pathogenic, risk factor
Assembly: GRCh37
Chromosome/Position: 17:32579788
OMIM Allelic Variant: 158105.0003
Last Evaluated: Jan 15, 2009
Review Status: no assertion criteria provided
Number of Submitters: 1
Clinical Significance: Pathogenic, risk factor
Assembly: GRCh37
Chromosome/Position: 17:32579788
OMIM Allelic Variant: 158105.0003
Last Evaluated: Jan 15, 2009
Review Status: no assertion criteria provided
Number of Submitters: 1
Clinical Significance: Pathogenic, risk factor
Assembly: GRCh37
Chromosome/Position: 17:32579788
OMIM Allelic Variant: 158105.0003
Last Evaluated: Jan 15, 2009
Review Status: no assertion criteria provided
Number of Submitters: 1
Clinical Significance: Pathogenic, risk factor
Assembly: GRCh37
Chromosome/Position: 17:32579788
OMIM Allelic Variant: 158105.0003
The data does not specify whether the genetic variant is autosomal recessive or autosomal dominant. For a definitive determination, refer to resources such as OMIM.
Clinically Significant Pathogenic, risk factor
Hetero
Gene:
ACTN3
Variant:
c.1729C>T
(p.Arg577Ter)
rsID: rs1815739
Ref Allele: C
Alt Allele: T
Freq: 40.0759%
ClinVar Submissions (1)
Last Evaluated: Oct 27, 2017
Review Status: no assertion criteria provided
Number of Submitters: 1
Clinical Significance: Conflicting interpretations of pathogenicity, Affects
Assembly: GRCh37
Chromosome/Position: 11:66328095
OMIM Allelic Variant: 102574.0001
Last Evaluated: Oct 27, 2017
Review Status: no assertion criteria provided
Number of Submitters: 1
Clinical Significance: Conflicting interpretations of pathogenicity, Affects
Assembly: GRCh37
Chromosome/Position: 11:66328095
OMIM Allelic Variant: 102574.0001
Last Evaluated: Oct 27, 2017
Review Status: no assertion criteria provided
Number of Submitters: 1
Clinical Significance: Conflicting interpretations of pathogenicity, Affects
Assembly: GRCh37
Chromosome/Position: 11:66328095
OMIM Allelic Variant: 102574.0001
The data does not specify whether the genetic variant is autosomal recessive or autosomal dominant. For a definitive determination, refer to resources such as OMIM. This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Clinically Significant Conflicting/Uncertain
Hetero
Gene:
GYG1
Variant:
c.248C>T
(p.Thr83Met)
rsID: rs267606858
Ref Allele: C
Alt Allele: T
CADD: 28.7
ClinVar Submissions (1)
Last Evaluated: Apr 01, 2012
Review Status: no assertion criteria provided
Number of Submitters: 1
Clinical Significance: Pathogenic
Assembly: GRCh37
Chromosome/Position: 3:148714193
OMIM Allelic Variant: 603942.0002
This individual has one copy of the genetic mutation, and because it's autosomal recessive, they are likely a carrier rather than manifesting the condition. Interpretation of carrier status should be backed by thorough research.
Clinically Significant Pathogenic
Hetero
Below are rare variants (frequency less than 1%) that were submitted to ClinVar. The data presented has no guarantees of reporting accuracy. Heterozygous variants are reported as yellow and homozygous variants as red. A red or yellow variant does not necessarily mean one has or carries a condition or disease. This is for research and educational purposes only.
Gene:
WDR19
Variant:
c.3667C>T
(p.Arg1223Cys)
rsID: rs201597047
Ref Allele: C
Alt Allele: T
Freq: 0.0399%rare
CADD: 33
ClinVar Submissions (3)
Cranioectodermal dysplasia (CED), a ciliopathy also known as Sensenbrenner syndrome, is a multisystem disorder with skeletal involvement (narrow thorax, shortened proximal limbs, and brachydactyly), ectodermal features (widely-spaced hypoplastic teeth, hypodontia, sparse hair, skin laxity, abnormal nails), joint laxity, growth retardation, and characteristic facial features (frontal bossing, low-set simple ears, high forehead, telecanthus/epicanthus, full cheeks, everted lower lip). Most affected children develop nephronophthisis that often leads to end-stage renal disease (ESRD) in infancy or childhood, a major cause of morbidity and mortality. Hepatic fibrosis and retinal dystrophy, other manifestations of ciliopathies, are also observed. Dolichocephaly, often secondary to sagittal craniosynostosis, is a primary manifestation that distinguishes CED from most other ciliopathies. Brain malformations and developmental delay may also occur.
Last Evaluated: Mar 21, 2018
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Uncertain significance
Assembly: GRCh37
Chromosome/Position: 4:39276529
Asphyxiating thoracic dystrophy, also known as Jeune syndrome, is an inherited disorder of bone growth characterized by a narrow chest, short ribs, shortened bones in the arms and legs, short stature, and extra fingers and toes (polydactyly). Additional skeletal abnormalities can include unusually shaped collarbones (clavicles) and pelvic bones, and and cone-shaped ends of the long bones in the arms and legs. Many infants with this condition are born with an extremely narrow, bell-shaped chest that can restrict the growth and expansion of the lungs. Life-threatening problems with breathing result, and people with asphyxiating thoracic dystrophy may live only into infancy or early childhood. However, in people who survive beyond the first few years, the narrow chest and related breathing problems can improve with age.Some people with asphyxiating thoracic dystrophy are born with less severe skeletal abnormalities and have only mild breathing difficulties, such as rapid breathing or shortness of breath. These individuals may live into adolescence or adulthood. After infancy, people with this condition may develop life-threatening kidney (renal) abnormalities that cause the kidneys to malfunction or fail. Heart defects and a narrowing of the airway (subglottic stenosis) are also possible. Other, less common features of asphyxiating thoracic dystrophy include liver disease, fluid-filled sacs (cysts) in the pancreas, dental abnormalities, and an eye disease called retinal dystrophy that can lead to vision loss.
Last Evaluated: Mar 21, 2018
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Uncertain significance
Assembly: GRCh37
Chromosome/Position: 4:39276529
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Mar 21, 2018
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Uncertain significance
Assembly: GRCh37
Chromosome/Position: 4:39276529
This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Conflicting/Uncertain
Hetero
Gene:
C3
Variant:
c.4855A>C
(p.Ser1619Arg)
rsID: rs2230210
Ref Allele: T
Alt Allele: G
Freq: 0.0399%rare
CADD: 22.5
ClinVar Submissions (1)
Hemolytic-uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney and other organs. The onset of atypical HUS (aHUS) ranges from the neonatal period to adulthood. Genetic aHUS accounts for an estimated 60% of all aHUS. Individuals with genetic aHUS frequently experience relapse even after complete recovery following the presenting episode; 60% of genetic aHUS progresses to end-stage renal disease (ESRD).
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 19:6678030
A rare genetic disorder with an autosomal recessive pattern of inheritance. It is caused by the ineffective or decreased biosynthesis of the third complement component, C3. C3 deficiency may also be acquired acutely post-infection or chronically from co-morbid autoimmune disorders. If C3 is adequately synthesized, its rapid depletion may result in a functional deficiency. Clinical signs of the inherited deficiency present within the first decade of life and are consistent with the signs of recurrent systemic infection or immune complex disease. Deficiency of serum C3 and its major cleavage product, C3b, will decrease the effective humoral immune response to encapsulated bacteria. Deficiency of C3 also impairs clearance of circulating immune complexes and therefore predisposes to rheumatic and renal disease.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 19:6678030
A nonspecific term denoting degeneration of the retinal pigment epithelium and/or retinal photoreceptor cells of the macula lutea.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 19:6678030
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Likely benign
Hetero
Gene:
ADGRV1
Variant:
c.3509A>G
(p.Tyr1170Cys)
rsID: rs188772875
Ref Allele: A
Alt Allele: G
Freq: 0.0599%rare
CADD: 24.2
ClinVar Submissions (4)
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Apr 27, 2018
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 4
Clinical Significance: Uncertain significance
Assembly: GRCh37
Chromosome/Position: 5:89948255
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Apr 27, 2018
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 4
Clinical Significance: Uncertain significance
Assembly: GRCh37
Chromosome/Position: 5:89948255
This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Conflicting/Uncertain
Hetero
Gene:
MYO1C
Variant:
c.754G>A
(p.Val252Ile)
rsID: rs117696188
Ref Allele: C
Alt Allele: T
Freq: 0.0799%rare
CADD: 23.9
ClinVar Submissions (1)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jan 03, 2018
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 17:1383868
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Likely benign
Hetero
Gene:
TRPM6
Variant:
c.5171C>T
(p.Thr1724Ile)
rsID: rs56290308
Ref Allele: G
Alt Allele: A
Freq: 0.0799%rare
CADD: 23
ClinVar Submissions (1)
Familial hypomagnesemia with secondary hypocalcemia is a rare autosomal recessive disorder characterized by very low serum magnesium levels. Hypocalcemia is a secondary consequence of parathyroid failure and parathyroid hormone resistance as a result of severe magnesium deficiency. The disease typically manifests during the first months of life with generalized convulsions or signs of increased neuromuscular excitability, such as muscle spasms or tetany. Untreated, the disease may be fatal or lead to severe neurologic damage. Treatment includes immediate administration of magnesium, usually intravenously, followed by life-long high-dose oral magnesium (review by Knoers, 2009). Genetic Heterogeneity of Hypomagnesemia A form of hypomagnesemia due to kidney defects and high urinary magnesium excretion associated with hypocalciuria (HOMG2; 154020) is caused by mutation in the FXYD2 gene (601814). Renal hypomagnesemia-3 (HOMG3; 248250), associated with hypercalciuria and nephrocalcinosis, is caused by mutation in the CLDN16 gene (603959). Renal hypomagnesemia-4 (HOMG4; 611718), which is normocalciuric, is caused by mutation in the EGF gene (131530). Renal hypomagnesemia-5 (HOMG5; 248190), associated with hypercalciuria, nephrocalcinosis, and severe ocular involvement, is caused by mutation in the CLDN19 gene (610036). Renal hypomagnesemia-6 (HOMG6; 613882) is caused by mutation in the CNNM2 gene (607803). Patients with Gitelman syndrome (263800) and Bartter syndrome (see 241200) also show hypomagnesemia, and steatorrhea and severe chronic diarrhea states, such as Crohn disease (see 226600) and Whipple disease, that can result in severe hypomagnesemia.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Uncertain significance
Assembly: GRCh37
Chromosome/Position: 9:77357506
This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Conflicting/Uncertain
Hetero
Gene:
RAPSN
Variant:
c.264C>A
(p.Asn88Lys)
rsID: rs104894299
Ref Allele: G
Alt Allele: T
Freq: 0.1198%rare
CADD: 26.6
ClinVar Submissions (13)
Last Evaluated: Jun 19, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 13
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:47469631
OMIM Allelic Variant: 601592.0001
Congenital myasthenic syndromes (designated as CMS throughout this entry) are characterized by fatigable weakness of skeletal muscle (e.g., ocular, bulbar, limb muscles) with onset at or shortly after birth or in early childhood; rarely, symptoms may not manifest until later in childhood. Cardiac and smooth muscle are usually not involved. Severity and course of disease are highly variable, ranging from minor symptoms to progressive disabling weakness. In some subtypes of CMS, myasthenic symptoms may be mild, but sudden severe exacerbations of weakness or even sudden episodes of respiratory insufficiency may be precipitated by fever, infections, or excitement. Major findings of the neonatal-onset subtype include: respiratory insufficiency with sudden apnea and cyanosis; feeding difficulties; poor suck and cry; choking spells; eyelid ptosis; and facial, bulbar, and generalized weakness. Arthrogryposis multiplex congenita may also be present. Stridor in infancy may be an important clue to CMS. Later childhood-onset subtypes show abnormal muscle fatigability with difficulty in activities such as running or climbing stairs; motor milestones may be delayed; fluctuating eyelid ptosis and fixed or fluctuating extraocular muscle weakness are common presentations.
Last Evaluated: Jun 19, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 13
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:47469631
OMIM Allelic Variant: 601592.0001
A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.
Last Evaluated: Jun 19, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 13
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:47469631
OMIM Allelic Variant: 601592.0001
Congenital myasthenic syndromes (designated as CMS throughout this entry) are characterized by fatigable weakness of skeletal muscle (e.g., ocular, bulbar, limb muscles) with onset at or shortly after birth or in early childhood; rarely, symptoms may not manifest until later in childhood. Cardiac and smooth muscle are usually not involved. Severity and course of disease are highly variable, ranging from minor symptoms to progressive disabling weakness. In some subtypes of CMS, myasthenic symptoms may be mild, but sudden severe exacerbations of weakness or even sudden episodes of respiratory insufficiency may be precipitated by fever, infections, or excitement. Major findings of the neonatal-onset subtype include: respiratory insufficiency with sudden apnea and cyanosis; feeding difficulties; poor suck and cry; choking spells; eyelid ptosis; and facial, bulbar, and generalized weakness. Arthrogryposis multiplex congenita may also be present. Stridor in infancy may be an important clue to CMS. Later childhood-onset subtypes show abnormal muscle fatigability with difficulty in activities such as running or climbing stairs; motor milestones may be delayed; fluctuating eyelid ptosis and fixed or fluctuating extraocular muscle weakness are common presentations.
Last Evaluated: Jun 19, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 13
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:47469631
OMIM Allelic Variant: 601592.0001
Congenital myasthenic syndromes (designated as CMS throughout this entry) are characterized by fatigable weakness of skeletal muscle (e.g., ocular, bulbar, limb muscles) with onset at or shortly after birth or in early childhood; rarely, symptoms may not manifest until later in childhood. Cardiac and smooth muscle are usually not involved. Severity and course of disease are highly variable, ranging from minor symptoms to progressive disabling weakness. In some subtypes of CMS, myasthenic symptoms may be mild, but sudden severe exacerbations of weakness or even sudden episodes of respiratory insufficiency may be precipitated by fever, infections, or excitement. Major findings of the neonatal-onset subtype include: respiratory insufficiency with sudden apnea and cyanosis; feeding difficulties; poor suck and cry; choking spells; eyelid ptosis; and facial, bulbar, and generalized weakness. Arthrogryposis multiplex congenita may also be present. Stridor in infancy may be an important clue to CMS. Later childhood-onset subtypes show abnormal muscle fatigability with difficulty in activities such as running or climbing stairs; motor milestones may be delayed; fluctuating eyelid ptosis and fixed or fluctuating extraocular muscle weakness are common presentations.
Last Evaluated: Jun 19, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 13
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:47469631
OMIM Allelic Variant: 601592.0001
Congenital myasthenic syndromes (designated as CMS throughout this entry) are characterized by fatigable weakness of skeletal muscle (e.g., ocular, bulbar, limb muscles) with onset at or shortly after birth or in early childhood; rarely, symptoms may not manifest until later in childhood. Cardiac and smooth muscle are usually not involved. Severity and course of disease are highly variable, ranging from minor symptoms to progressive disabling weakness. In some subtypes of CMS, myasthenic symptoms may be mild, but sudden severe exacerbations of weakness or even sudden episodes of respiratory insufficiency may be precipitated by fever, infections, or excitement. Major findings of the neonatal-onset subtype include: respiratory insufficiency with sudden apnea and cyanosis; feeding difficulties; poor suck and cry; choking spells; eyelid ptosis; and facial, bulbar, and generalized weakness. Arthrogryposis multiplex congenita may also be present. Stridor in infancy may be an important clue to CMS. Later childhood-onset subtypes show abnormal muscle fatigability with difficulty in activities such as running or climbing stairs; motor milestones may be delayed; fluctuating eyelid ptosis and fixed or fluctuating extraocular muscle weakness are common presentations.
Last Evaluated: Jun 19, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 13
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:47469631
OMIM Allelic Variant: 601592.0001
The fetal akinesia deformation sequence (FADS) refers to a clinically and genetically heterogeneous constellation of features including fetal akinesia, intrauterine growth retardation, arthrogryposis, and developmental anomalies, including lung hypoplasia, cleft palate, and cryptorchidism (Vogt et al., 2009). It shows phenotypic overlap with the lethal form of multiple pterygium syndrome (see 253290).
Last Evaluated: Jun 19, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 13
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:47469631
OMIM Allelic Variant: 601592.0001
The fetal akinesia deformation sequence (FADS) refers to a clinically and genetically heterogeneous constellation of features including fetal akinesia, intrauterine growth retardation, arthrogryposis, and developmental anomalies, including lung hypoplasia, cleft palate, and cryptorchidism (Vogt et al., 2009). It shows phenotypic overlap with the lethal form of multiple pterygium syndrome (see 253290).
Last Evaluated: Jun 19, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 13
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:47469631
OMIM Allelic Variant: 601592.0001
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Jun 19, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 13
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 11:47469631
OMIM Allelic Variant: 601592.0001
This individual has one copy of the genetic mutation, and because it's autosomal recessive, they are likely a carrier rather than manifesting the condition. This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
High clinical importance, Likely pathogenic — Causes congenital myasthenic syndrome in a recessive manner (when homozygous or combined with another deleterious variant in the same gene).
Clinically Significant Conflicting/Uncertain
Hetero
Gene:
CNGB1
Variant:
c.1382C>T
(p.Thr461Met)
rsID: rs147593839
Ref Allele: G
Alt Allele: A
Freq: 0.1797%rare
CADD: 24.9
ClinVar Submissions (2)
A group of disorders involving predominantly the posterior portion of the ocular fundus, due to degeneration in the sensory layer of the RETINA; RETINAL PIGMENT EPITHELIUM; BRUCH MEMBRANE; CHOROID; or a combination of these tissues.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 2
Clinical Significance: Uncertain significance
Assembly: GRCh37
Chromosome/Position: 16:57965773
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 2
Clinical Significance: Uncertain significance
Assembly: GRCh37
Chromosome/Position: 16:57965773
This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Conflicting/Uncertain
Hetero
Gene:
TP63
Variant:
c.1531C>A
(p.Pro511Thr)
rsID: rs148076109
Ref Allele: C
Alt Allele: A
Freq: 0.2596%rare
CADD: 24.1
ClinVar Submissions (3)
Last Evaluated: Nov 16, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 3:189607152
A condition in which middle parts of the hands and/or feet (digits and meta-carpals and -tarsals) are missing giving a cleft appearance. The severity is very variable ranging from slightly hypoplastic 3rd toe/fingers over absent 2nd or 3rd toes/fingers as far as oligo- or monodactyl hands and/or feet.
Last Evaluated: Nov 16, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 3:189607152
Last Evaluated: Nov 16, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 3:189607152
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Nov 16, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 3:189607152
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Likely benign
Hetero
Gene:
STX11
Variant:
c.799G>A
(p.Val267Met)
rsID: rs45574234
Ref Allele: G
Alt Allele: A
Freq: 0.2596%rare
CADD: 22.9
ClinVar Submissions (2)
Familial hemophagocytic lymphohistiocytosis (FHL) is characterized by proliferation and infiltration of hyperactivated macrophages and T-lymphocytes manifesting as acute illness with prolonged fever, cytopenias, and hepatosplenomegaly. Onset is typically within the first months or years of life and, on occasion, in utero, although later childhood or adult onset is more common than previously suspected. Neurologic abnormalities may be present initially or may develop later; they may include increased intracranial pressure, irritability, neck stiffness, hypotonia, hypertonia, convulsions, cranial nerve palsies, ataxia, hemiplegia, quadriplegia, blindness, and coma. Rash and lymphadenopathy are less common. Other findings include liver dysfunction and bone marrow hemophagocytosis. The median survival of children with typical FHL, without treatment, is less than two months; progression of hemophagocytic lymphohistiocytosis and infection account for the majority of deaths in untreated individuals.
Last Evaluated: Nov 15, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 6:144508563
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Nov 15, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 6:144508563
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
BBS10
Variant:
c.424G>A
(p.Asp142Asn)
rsID: rs142863601
Ref Allele: C
Alt Allele: T
Freq: 0.2796%rare
CADD: 27.8
ClinVar Submissions (8)
Bardet-Biedl syndrome (BBS) is characterized by rod-cone dystrophy, truncal obesity, postaxial polydactyly, cognitive impairment, male hypogonadotropic hypogonadism, complex female genitourinary malformations, and renal abnormalities. The visual prognosis for children with BBS is poor. Night blindness is usually evident by age seven to eight years; the mean age of legal blindness is 15.5 years. Birth weight is usually normal, but significant weight gain begins within the first year and becomes a lifelong issue for most individuals. A majority of individuals have significant learning difficulties; a minority have severe impairment on IQ testing. Renal disease is a major cause of morbidity and mortality.
Last Evaluated: Jul 26, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 12:76741341
Bardet-Biedl syndrome (BBS) is characterized by rod-cone dystrophy, truncal obesity, postaxial polydactyly, cognitive impairment, male hypogonadotropic hypogonadism, complex female genitourinary malformations, and renal abnormalities. The visual prognosis for children with BBS is poor. Night blindness is usually evident by age seven to eight years; the mean age of legal blindness is 15.5 years. Birth weight is usually normal, but significant weight gain begins within the first year and becomes a lifelong issue for most individuals. A majority of individuals have significant learning difficulties; a minority have severe impairment on IQ testing. Renal disease is a major cause of morbidity and mortality.
Last Evaluated: Jul 26, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 12:76741341
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Jul 26, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 12:76741341
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jul 26, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 12:76741341
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
LAMA2
Variant:
c.4487C>T
(p.Ala1496Val)
rsID: rs147077184
Ref Allele: C
Alt Allele: T
Freq: 0.2796%rare
CADD: 24
ClinVar Submissions (10)
The clinical manifestations of LAMA2-related muscular dystrophy (LAMA2 MD) range from severe, early-onset congenital muscular dystrophy (CMD) – referred to as early-onset LAMA2-related muscular dystrophy (LAMA2 MD) in this GeneReview – to mild, later childhood-onset limb-girdle type muscular dystrophy – referred to here as late-onset LAMA2-related muscular dystrophy (LAMA2 MD). Children with early-onset LAMA2 MD have profound hypotonia with muscle weakness evident at birth or within the first six months of life, poor spontaneous movements with contractures of the large joints, and weak cry often associated with respiratory failure. Feeding difficulties with failure to thrive, aspiration, and recurrent chest infections are typical. Progressive scoliosis starting in childhood is common. Seizures and, less often, cardiac involvement can occur. Typically, individuals with early-onset LAMA2 MD do not achieve independent ambulation. Intellect is usually normal. Those with limb-girdle type muscular dystrophy have later onset of proximal muscle weakness and delayed motor milestones, but achieve independent ambulation; they may develop a rigid spine syndrome with joint contractures. Progressive respiratory insufficiency and scoliosis can occur.
Last Evaluated: Oct 05, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 10
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 6:129670493
OMIM Allelic Variant: 156225.0019
The clinical manifestations of LAMA2-related muscular dystrophy (LAMA2 MD) range from severe, early-onset congenital muscular dystrophy (CMD) – referred to as early-onset LAMA2-related muscular dystrophy (LAMA2 MD) in this GeneReview – to mild, later childhood-onset limb-girdle type muscular dystrophy – referred to here as late-onset LAMA2-related muscular dystrophy (LAMA2 MD). Children with early-onset LAMA2 MD have profound hypotonia with muscle weakness evident at birth or within the first six months of life, poor spontaneous movements with contractures of the large joints, and weak cry often associated with respiratory failure. Feeding difficulties with failure to thrive, aspiration, and recurrent chest infections are typical. Progressive scoliosis starting in childhood is common. Seizures and, less often, cardiac involvement can occur. Typically, individuals with early-onset LAMA2 MD do not achieve independent ambulation. Intellect is usually normal. Those with limb-girdle type muscular dystrophy have later onset of proximal muscle weakness and delayed motor milestones, but achieve independent ambulation; they may develop a rigid spine syndrome with joint contractures. Progressive respiratory insufficiency and scoliosis can occur.
Last Evaluated: Oct 05, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 10
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 6:129670493
OMIM Allelic Variant: 156225.0019
Merosin-deficient congenital muscular dystrophy is an autosomal recessive form of muscular dystrophy characterized by muscle weakness apparent at birth or in the first 6 months of life. Patients show hypotonia, poor suck and cry, and delayed motor development; most never achieve independent ambulation. Most patients also have periventricular white matter abnormalities on brain imaging, but mental retardation and/or seizures occur only rarely (summary by Xiong et al., 2015).
Last Evaluated: Oct 05, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 10
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 6:129670493
OMIM Allelic Variant: 156225.0019
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Oct 05, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 10
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 6:129670493
OMIM Allelic Variant: 156225.0019
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Oct 05, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 10
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 6:129670493
OMIM Allelic Variant: 156225.0019
This individual has one copy of the genetic mutation, and because it's autosomal recessive, they are likely a carrier rather than manifesting the condition. This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Clinically Significant Conflicting/Uncertain
Hetero
Gene:
POLD1
Variant:
c.88C>T
(p.Arg30Trp)
rsID: rs3218772
Ref Allele: C
Alt Allele: T
Freq: 0.3794%rare
CADD: 15.67
ClinVar Submissions (8)
Last Evaluated: Dec 01, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 19:50902196
The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.
Last Evaluated: Dec 01, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 19:50902196
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Dec 01, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 19:50902196
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Dec 01, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 19:50902196
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
TTN
Variant:
c.4034G>A
(p.Gly1345Asp)
rsID: rs36021856
Ref Allele: C
Alt Allele: T
Freq: 0.3794%rare
CADD: 23
ClinVar Submissions (8)
Last Evaluated: Nov 30, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179643775
Last Evaluated: Nov 30, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179643775
Last Evaluated: Nov 30, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179643775
Udd distal myopathy is characterized by weakness of ankle dorsiflexion and inability to walk on the heels after age 35 years. Disease progression is slow and muscle weakness remains confined to the anterior tibial muscles. The long toe extensors become clinically involved after ten to 20 years, leading to foot drop and clumsiness when walking. In the mildest form, Udd distal myopathy can remain unnoticed even in the elderly.
Last Evaluated: Nov 30, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179643775
Hereditary myopathy with early respiratory failure (HMERF) is a slowly progressive myopathy that typically begins in the third to fifth decades of life. The usual presenting findings are gait disturbance relating to distal leg weakness or nocturnal respiratory symptoms due to respiratory muscle weakness. Weakness eventually generalizes and affects both proximal and distal muscles. Most affected individuals require walking aids within a few years of onset; some progress to wheelchair dependence and require nocturnal noninvasive ventilatory support. The disease course varies even among individuals within the same family: some remain ambulant until their 70s whereas others may require ventilator support in their 40s.
Last Evaluated: Nov 30, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179643775
A condition in which the myocardium is hypertrophied without an obvious cause. The hypertrophy is generally asymmetric and may be associated with obstruction of the ventricular outflow tract.
Last Evaluated: Nov 30, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179643775
Last Evaluated: Nov 30, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179643775
Limb-girdle muscular dystrophy is a term for a group of diseases that cause weakness and wasting of the muscles in the arms and legs. The muscles most affected are those closest to the body (proximal muscles), specifically the muscles of the shoulders, upper arms, pelvic area, and thighs.The severity, age of onset, and features of limb-girdle muscle dystrophy vary among the many subtypes of this condition and may be inconsistent even within the same family. Signs and symptoms may first appear at any age and generally worsen with time, although in some cases they remain mild.In the early stages of limb-girdle muscular dystrophy, affected individuals may have an unusual walking gait, such as waddling or walking on the balls of their feet, and may also have difficulty running. They may need to use their arms to press themselves up from a squatting position because of their weak thigh muscles. As the condition progresses, people with limb-girdle muscular dystrophy may eventually require wheelchair assistance.Muscle wasting may cause changes in posture or in the appearance of the shoulder, back, and arm. In particular, weak shoulder muscles tend to make the shoulder blades (scapulae) "stick out" from the back, a sign known as scapular winging. Affected individuals may also have an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Some develop joint stiffness (contractures) that can restrict movement in their hips, knees, ankles, or elbows. Overgrowth (hypertrophy) of the calf muscles occurs in some people with limb-girdle muscular dystrophy.Weakening of the heart muscle (cardiomyopathy) occurs in some forms of limb-girdle muscular dystrophy. Some affected individuals experience mild to severe breathing problems related to the weakness of muscles needed for breathing. In some cases, the breathing problems are severe enough that affected individuals need to use a machine to help them breathe (mechanical ventilation).Intelligence is generally unaffected in limb-girdle muscular dystrophy; however, developmental delay and intellectual disability have been reported in rare forms of the disorder.
Last Evaluated: Nov 30, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179643775
Salih myopathy is characterized by muscle weakness (manifest during the neonatal period or in early infancy) and delayed motor development; children acquire independent walking between age 20 months and four years. In the first decade of life, global motor performances are stable or tend to improve. Moderate joint and neck contractures and spinal rigidity may start in the first decade but become more obvious in the second decade. Scoliosis develops after age 11 years. Cardiac dysfunction starts between ages five and 16 years, progresses rapidly, and leads to death between ages eight and 20 years, usually from heart rhythm disturbances.
Last Evaluated: Nov 30, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179643775
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Nov 30, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179643775
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
TTN
Variant:
c.99083C>T
(p.Thr33028Ile)
rsID: rs55842557
Ref Allele: G
Alt Allele: A
Freq: 0.3794%rare
CADD: 23.3
ClinVar Submissions (8)
Last Evaluated: Nov 30, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179393691
Last Evaluated: Nov 30, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179393691
Last Evaluated: Nov 30, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179393691
Udd distal myopathy is characterized by weakness of ankle dorsiflexion and inability to walk on the heels after age 35 years. Disease progression is slow and muscle weakness remains confined to the anterior tibial muscles. The long toe extensors become clinically involved after ten to 20 years, leading to foot drop and clumsiness when walking. In the mildest form, Udd distal myopathy can remain unnoticed even in the elderly.
Last Evaluated: Nov 30, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179393691
Hereditary myopathy with early respiratory failure (HMERF) is a slowly progressive myopathy that typically begins in the third to fifth decades of life. The usual presenting findings are gait disturbance relating to distal leg weakness or nocturnal respiratory symptoms due to respiratory muscle weakness. Weakness eventually generalizes and affects both proximal and distal muscles. Most affected individuals require walking aids within a few years of onset; some progress to wheelchair dependence and require nocturnal noninvasive ventilatory support. The disease course varies even among individuals within the same family: some remain ambulant until their 70s whereas others may require ventilator support in their 40s.
Last Evaluated: Nov 30, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179393691
A condition in which the myocardium is hypertrophied without an obvious cause. The hypertrophy is generally asymmetric and may be associated with obstruction of the ventricular outflow tract.
Last Evaluated: Nov 30, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179393691
Last Evaluated: Nov 30, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179393691
Limb-girdle muscular dystrophy is a term for a group of diseases that cause weakness and wasting of the muscles in the arms and legs. The muscles most affected are those closest to the body (proximal muscles), specifically the muscles of the shoulders, upper arms, pelvic area, and thighs.The severity, age of onset, and features of limb-girdle muscle dystrophy vary among the many subtypes of this condition and may be inconsistent even within the same family. Signs and symptoms may first appear at any age and generally worsen with time, although in some cases they remain mild.In the early stages of limb-girdle muscular dystrophy, affected individuals may have an unusual walking gait, such as waddling or walking on the balls of their feet, and may also have difficulty running. They may need to use their arms to press themselves up from a squatting position because of their weak thigh muscles. As the condition progresses, people with limb-girdle muscular dystrophy may eventually require wheelchair assistance.Muscle wasting may cause changes in posture or in the appearance of the shoulder, back, and arm. In particular, weak shoulder muscles tend to make the shoulder blades (scapulae) "stick out" from the back, a sign known as scapular winging. Affected individuals may also have an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Some develop joint stiffness (contractures) that can restrict movement in their hips, knees, ankles, or elbows. Overgrowth (hypertrophy) of the calf muscles occurs in some people with limb-girdle muscular dystrophy.Weakening of the heart muscle (cardiomyopathy) occurs in some forms of limb-girdle muscular dystrophy. Some affected individuals experience mild to severe breathing problems related to the weakness of muscles needed for breathing. In some cases, the breathing problems are severe enough that affected individuals need to use a machine to help them breathe (mechanical ventilation).Intelligence is generally unaffected in limb-girdle muscular dystrophy; however, developmental delay and intellectual disability have been reported in rare forms of the disorder.
Last Evaluated: Nov 30, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179393691
Salih myopathy is characterized by muscle weakness (manifest during the neonatal period or in early infancy) and delayed motor development; children acquire independent walking between age 20 months and four years. In the first decade of life, global motor performances are stable or tend to improve. Moderate joint and neck contractures and spinal rigidity may start in the first decade but become more obvious in the second decade. Scoliosis develops after age 11 years. Cardiac dysfunction starts between ages five and 16 years, progresses rapidly, and leads to death between ages eight and 20 years, usually from heart rhythm disturbances.
Last Evaluated: Nov 30, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179393691
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Nov 30, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 8
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:179393691
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
DNAH8
Variant:
c.5490C>A
(p.Asp1830Glu)
rsID: rs45519938
Ref Allele: C
Alt Allele: A
Freq: 0.3994%rare
CADD: 23.4
ClinVar Submissions (1)
Primary ciliary dyskinesia (PCD) is associated with situs abnormalities, abnormal sperm motility, and abnormal ciliary structure and function that result in retention of mucus and bacteria in the respiratory tract leading to chronic otosinopulmonary disease. More than 75% of full-term neonates with PCD have "neonatal respiratory distress" requiring supplemental oxygen for days to weeks. Chronic airway infection, apparent in early childhood, results in bronchiectasis that is almost uniformly present in adulthood. Nasal congestion and sinus infections, apparent in early childhood, persist through adulthood. Chronic/recurrent ear infection, apparent in most young children, can be associated with transient or later irreversible hearing loss. Situs inversus totalis (mirror-image reversal of all visceral organs with no apparent physiologic consequences) is present in 40%-50% of individuals with PCD; heterotaxy (discordance of right and left patterns of ordinarily asymmetric structures that can be associated with significant malformations) is present in approximately 12%. Virtually all males with PCD are infertile as a result of abnormal sperm motility.
Last Evaluated: Jul 24, 2017
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 6:38820493
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
COL4A4
Variant:
c.2996G>A
(p.Gly999Glu)
rsID: rs13027659
Ref Allele: C
Alt Allele: T
Freq: 0.4593%rare
CADD: 24.6
ClinVar Submissions (4)
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Jan 20, 2018
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 4
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:227915847
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jan 20, 2018
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 4
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:227915847
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Low clinical importance, Uncertain benign — This variant is causative for Benign Familial Hematuria (thin membrane basement disease). While this variant is benign, it is useful in differentiating glomerular hematuria from Alport Syndrome.
Benign/Likely benign
Hetero
Gene:
USH2A
Variant:
c.13297G>T
(p.Val4433Leu)
rsID: rs111033381
Ref Allele: C
Alt Allele: A
Freq: 0.4992%rare
CADD: 13.01
ClinVar Submissions (3)
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Jul 22, 2014
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 1:215847956
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jul 22, 2014
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 1:215847956
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
DDHD1
Variant:
c.136G>A
(p.Gly46Ser)
rsID: rs61985140
Ref Allele: C
Alt Allele: T
Freq: 0.4992%rare
CADD: 15.27
ClinVar Submissions (2)
SPG28 is an autosomal recessive neurodegenerative disorder characterized by early-onset, slowly progressive lower-limb spasticity resulting in walking difficulties. Some patients also have distal sensory impairment (summary by Tesson et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800.
Last Evaluated: Jul 12, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 14:53619681
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jul 12, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 14:53619681
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
ITK
Variant:
c.*1361G>A
rsID: rs79627475
Ref Allele: G
Alt Allele: A
Freq: 0.5192%rare
CADD: 3.881
ClinVar Submissions (1)
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Uncertain significance
Assembly: GRCh37
Chromosome/Position: 5:156681049
This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Conflicting/Uncertain
Hetero
Gene:
CUL7
Variant:
c.4762C>A
(p.Leu1588Ile)
rsID: rs147493246
Ref Allele: G
Alt Allele: T
Freq: 0.5591%rare
CADD: 29.8
ClinVar Submissions (3)
Three M syndrome is characterized by severe pre- and postnatal growth deficiency (final height 5-6 SD below the mean; i.e., 120-130 cm), characteristic facies, and normal intelligence. Additional features of three M syndrome include short broad neck, prominent trapezii, deformed sternum, short thorax, square shoulders, winged scapulae, hyperlordosis, short fifth fingers, prominent heels, and loose joints. Males with three M syndrome have hypogonadism and occasionally hypospadias.
Last Evaluated: May 09, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 3
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 6:43006016
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: May 09, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 3
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 6:43006016
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: May 09, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 3
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 6:43006016
This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Conflicting/Uncertain
Hetero
Gene:
PDLIM3
Variant:
c.734C>T
(p.Thr245Ile)
rsID: rs62347360
Ref Allele: G
Alt Allele: A
Freq: 0.5591%rare
CADD: 15.3
ClinVar Submissions (5)
Last Evaluated: Jul 26, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 5
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 4:186427735
A condition in which the myocardium is hypertrophied without an obvious cause. The hypertrophy is generally asymmetric and may be associated with obstruction of the ventricular outflow tract.
Last Evaluated: Jul 26, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 5
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 4:186427735
Familial dilated cardiomyopathy is a genetic form of heart disease. It occurs when heart (cardiac) muscle becomes thin and weakened in at least one chamber of the heart, causing the open area of the chamber to become enlarged (dilated). As a result, the heart is unable to pump blood as efficiently as usual. To compensate, the heart attempts to increase the amount of blood being pumped through the heart, leading to further thinning and weakening of the cardiac muscle. Over time, this condition results in heart failure.It usually takes many years for symptoms of familial dilated cardiomyopathy to cause health problems. They typically begin in mid-adulthood, but can occur at any time from infancy to late adulthood. Signs and symptoms of familial dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath (dyspnea), extreme tiredness (fatigue), fainting episodes (syncope), and swelling of the legs and feet. In some cases, the first sign of the disorder is sudden cardiac death. The severity of the condition varies among affected individuals, even in members of the same family.
Last Evaluated: Jul 26, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 5
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 4:186427735
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Jul 26, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 5
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 4:186427735
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jul 26, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 5
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 4:186427735
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
MYH7
Variant:
c.597A>G
(p.Ala199=)
rsID: rs2069541
Ref Allele: T
Alt Allele: C
Freq: 0.5791%rare
CADD: 10.37
ClinVar Submissions (7)
A disease of the heart muscle or myocardium proper. Cardiomyopathies may be classified as either primary or secondary, on the basis of etiology, or on the pathophysiology of the lesion: hypertrophic, dilated, or restrictive.
Last Evaluated: Aug 15, 2017
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 14:23901012
Last Evaluated: Aug 15, 2017
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 14:23901012
Last Evaluated: Aug 15, 2017
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 14:23901012
A condition in which the myocardium is hypertrophied without an obvious cause. The hypertrophy is generally asymmetric and may be associated with obstruction of the ventricular outflow tract.
Last Evaluated: Aug 15, 2017
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 14:23901012
An uncommon congenital abnormality where the left ventricular myocardium fails to compact during embryonic development, leading to cardiomyopathy with a variable degree of ventricular dysfunction. There is genetic heterogeneity and phenotypic variability. Characteristically, there are typically deep trabeculations in the noncompacted area, with varying proportions of the LV myocardium compacted. LV noncompaction is associated with rhythm abnormalities including Wolff-Parkinson-White syndrome, conduction defects, and ventricular tachyarrhythmias.
Last Evaluated: Aug 15, 2017
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 14:23901012
Laing distal myopathy is characterized by early-onset weakness (usually before age 5 years) that initially involves the dorsiflexors of the ankles and great toes and then the finger extensors, especially those of the third and fourth fingers. Weakness of the neck flexors is seen in most affected individuals and mild facial weakness is often present. After distal weakness has been present for more than ten years, mild proximal weakness may be observed. Life expectancy is normal.
Last Evaluated: Aug 15, 2017
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 14:23901012
Myosin storage myopathy, also known as hyaline body myopathy, is a congenital myopathy characterized by the accumulation of ATPase and antibody positive myosin in hyaline subsarcolemmal bodies in type I muscle fibers. The clinical features are variable, with different patients displaying proximal, scapuloperoneal, or generalized weakness and progressive or nonprogressive courses (summary by Dye et al., 2006).
Last Evaluated: Aug 15, 2017
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 14:23901012
Last Evaluated: Aug 15, 2017
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 14:23901012
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Aug 15, 2017
Review Status: reviewed by expert panel
Number of Submitters: 7
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 14:23901012
Expert Reviewed Benign
Hetero
Gene:
KCNT1
Variant:
c.2210C>T
(p.Thr737Met)
rsID: rs61744696
Ref Allele: C
Alt Allele: T
Freq: 0.5791%rare
CADD: 16.68
ClinVar Submissions (6)
KCNT1-related epilepsy is most often associated with two phenotypes: epilepsy of infancy with migrating focal seizures (EIMFS) and autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). EIMFS is characterized by seizures, typically focal and asynchronous, beginning in the first six months of life with associated developmental plateau or regression. Autonomic manifestations (e.g., perioral cyanosis, flushing, apnea) are common. Seizures are intractable to multiple anticonvulsants and progress to become nearly continuous by age six to nine months. ADNFLE is characterized by clusters of nocturnal motor seizures that vary from simple arousals to hyperkinetic events with tonic or dystonic features. Individuals with KCNT1-related ADNFLE are more likely to develop seizures at a younger age, have cognitive comorbidity, and display psychiatric and behavioral problems than individuals with ADNFLE due to other causes. Less common seizure phenotypes in individuals with KCNT1-related epilepsy include West syndrome, Ohtahara syndrome, early myoclonic encephalopathy, leukodystrophy and/or leukoencephalopathy, focal epilepsy, and multifocal epilepsy. Additional neurologic features include hypotonia, microcephaly developing by age 12 months, strabismus, profound global developmental delay, and additional movement disorders. Other systemic manifestations including pulmonary hemorrhage caused by prominent systemic-to-pulmonary collateral arteries or cardiac arrhythmia have been reported.
Last Evaluated: Aug 14, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 6
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 9:138664762
Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is characterized by clusters of nocturnal motor seizures, which are often stereotyped and brief (5 seconds to 5 minutes). They vary from simple arousals from sleep to dramatic, often bizarre hyperkinetic events with tonic or dystonic features. Affected individuals may experience aura. Retained awareness during seizures is common. A minority of individuals experience daytime seizures. Onset ranges from infancy to adulthood. About 80% of individuals develop ADNFLE in the first two decades of life; mean age of onset is ten years. Clinical neurologic examination is normal and intellect is usually preserved, but reduced intellect, psychiatric comorbidity, or cognitive deficits may occur. Within a family, the manifestations of the disorder may vary considerably. ADNFLE is lifelong but not progressive. As an individual reaches middle age, attacks may become milder and less frequent.
Last Evaluated: Aug 14, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 6
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 9:138664762
Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or "seizure disorder."
Last Evaluated: Aug 14, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 6
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 9:138664762
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Aug 14, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 6
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 9:138664762
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
OCA2
Variant:
c.574-19A>G
rsID: rs145242923
Ref Allele: T
Alt Allele: C
Freq: 0.619%rare
CADD: 2.917
ClinVar Submissions (2)
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Oct 27, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 2
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 15:28267738
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Oct 27, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 2
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 15:28267738
This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Conflicting/Uncertain
Hetero
Gene:
MYO7A
Variant:
c.*560C>T
rsID: rs35776264
Ref Allele: C
Alt Allele: T
Freq: 0.619%rare
CADD: 0.691
ClinVar Submissions (1)
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 11:76926301
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 11:76926301
Usher syndrome is a condition characterized by partial or total hearing loss and vision loss that worsens over time. The hearing loss is classified as sensorineural, which means that it is caused by abnormalities of the inner ear. The loss of vision is caused by an eye disease called retinitis pigmentosa (RP), which affects the layer of light-sensitive tissue at the back of the eye (the retina). Vision loss occurs as the light-sensing cells of the retina gradually deteriorate. Night vision loss begins first, followed by blind spots that develop in the side (peripheral) vision. Over time, these blind spots enlarge and merge to produce tunnel vision. In some cases, vision is further impaired by clouding of the lens of the eye (cataracts). However, many people with retinitis pigmentosa retain some central vision throughout their lives.Researchers have identified three major types of Usher syndrome, designated as types I, II, and III. These types are distinguished by the severity of hearing loss, the presence or absence of balance problems, and the age at which signs and symptoms appear. The types are further divided into subtypes based on their genetic cause.Most individuals with Usher syndrome type I are born with severe to profound hearing loss. Progressive vision loss caused by retinitis pigmentosa becomes apparent in childhood. This type of Usher syndrome also causes abnormalities of the vestibular system, which is the part of the inner ear that helps maintain the body's balance and orientation in space. As a result of the vestibular abnormalities, children with the condition have trouble with balance. They begin sitting independently and walking later than usual, and they may have difficulty riding a bicycle and playing certain sports.Usher syndrome type II is characterized by hearing loss from birth and progressive vision loss that begins in adolescence or adulthood. The hearing loss associated with this form of Usher syndrome ranges from mild to severe and mainly affects the ability to hear high-frequency sounds. For example, it is difficult for affected individuals to hear high, soft speech sounds, such as those of the letters d and t. The degree of hearing loss varies within and among families with this condition, and it may become more severe over time. Unlike the other forms of Usher syndrome, type II is not associated with vestibular abnormalities that cause difficulties with balance.People with Usher syndrome type III experience hearing loss and vision loss beginning somewhat later in life. Unlike the other forms of Usher syndrome, type III is usually associated with normal hearing at birth. Hearing loss typically begins during late childhood or adolescence, after the development of speech, and becomes more severe over time. By middle age, most affected individuals have profound hearing loss. Vision loss caused by retinitis pigmentosa also develops in late childhood or adolescence. Some people with Usher syndrome type III develop vestibular abnormalities that cause problems with balance.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 11:76926301
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Likely benign
Hetero
Gene:
ABCB7
Variant:
c.249+1G>A
rsID: rs61323727
Ref Allele: C
Alt Allele: T
Freq: 0.6358%rare
ClinVar Submissions (3)
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 3
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: X:74334588
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 3
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: X:74334588
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 3
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: X:74334588
This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Conflicting/Uncertain
Homo
Gene:
ITK
Variant:
c.769-13C>T
rsID: rs56100638
Ref Allele: C
Alt Allele: T
Freq: 0.6589%rare
CADD: 9.846
ClinVar Submissions (3)
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 5:156665106
Lymphoproliferative syndrome-1 is an autosomal recessive primary immunodeficiency characterized by onset in early childhood of Epstein-Barr virus (EBV)-associated immune dysregulation, manifest as lymphoma, lymphomatoid granulomatosis, hemophagocytic lymphohistiocytosis, Hodgkin disease, and/or hypogammaglobulinemia. Autoimmune disorders, such as autoimmune hemolytic anemia or renal disease, may also occur. Patients show a high EBV viral load and decreased invariant natural killer T cells. It is unknown whether patients with ITK mutations are intrinsically susceptible to development of lymphoma or dysgammaglobulinemia in the absence of EBV infection (summary by Stepensky et al., 2011; Linka et al., 2012). For a discussion of genetic heterogeneity of lymphoproliferative syndrome, see XLP1 (308240).
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 5:156665106
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
FANCF
Variant:
c.825G>A
(p.Leu275=)
rsID: rs36045913
Ref Allele: C
Alt Allele: T
Freq: 0.6789%rare
CADD: 14.98
ClinVar Submissions (3)
Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk for malignancy. Physical abnormalities, present in approximately 75% of affected individuals, include one or more of the following: short stature, abnormal skin pigmentation, skeletal malformations of the upper and lower limbs, microcephaly, and ophthalmic and genitourinary tract anomalies. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. The incidence of acute myeloid leukemia is 13% by age 50 years. Solid tumors – particularly of the head and neck, skin, gastrointestinal tract, and genitourinary tract – are more common in individuals with FA.
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 11:22646532
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 11:22646532
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
CYSLTR2
Variant:
c.601A>G
(p.Met201Val)
rsID: rs41347648
Ref Allele: A
Alt Allele: G
Freq: 0.6989%rare
CADD: 10.39
ClinVar Submissions (1)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Oct 04, 2015
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Uncertain significance
Assembly: GRCh37
Chromosome/Position: 13:49281554
This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Conflicting/Uncertain
Hetero
Gene:
LOXHD1
Variant:
c.3269G>A
(p.Arg1090Gln)
rsID: rs118174674
Ref Allele: C
Alt Allele: T
Freq: 0.7189%rare
CADD: 18.84
ClinVar Submissions (4)
Last Evaluated: Nov 29, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 4
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 18:44137400
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Nov 29, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 4
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 18:44137400
This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Conflicting/Uncertain
Hetero
Gene:
SOS1
Variant:
c.*1731A>G
rsID: rs79270739
Ref Allele: T
Alt Allele: C
Freq: 0.7189%rare
CADD: 13.61
ClinVar Submissions (1)
Generalized or localized diffuse fibrous overgrowth of the gingival tissue, usually transmitted as an autosomal dominant trait, but some cases are idiopathic and others produced by drugs. The enlarged gingiva is pink, firm, and has a leather-like consistency with a minutely pebbled surface and in severe cases the teeth are almost completely covered and the enlargement projects into the oral vestibule. (Dorland, 28th ed)
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 2:39211234
Noonan syndrome (NS) is characterized by characteristic facies, short stature, congenital heart defect, and developmental delay of variable degree. Other findings can include broad or webbed neck, unusual chest shape with superior pectus carinatum and inferior pectus excavatum, cryptorchidism, varied coagulation defects, lymphatic dysplasias, and ocular abnormalities. Although birth length is usually normal, final adult height approaches the lower limit of normal. Congenital heart disease occurs in 50%-80% of individuals. Pulmonary valve stenosis, often with dysplasia, is the most common heart defect and is found in 20%-50% of individuals. Hypertrophic cardiomyopathy, found in 20%-30% of individuals, may be present at birth or develop in infancy or childhood. Other structural defects include atrial and ventricular septal defects, branch pulmonary artery stenosis, and tetralogy of Fallot. Up to one fourth of affected individuals have mild intellectual disability, and language impairments in general are more common in NS than in the general population.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 2:39211234
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Likely benign
Hetero
Gene:
MUSK
Variant:
c.-82T>C
rsID: rs41279047
Ref Allele: T
Alt Allele: C
Freq: 0.7388%rare
CADD: 16.12
ClinVar Submissions (1)
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Uncertain significance
Assembly: GRCh37
Chromosome/Position: 9:113431103
This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Conflicting/Uncertain
Hetero
Gene:
MPC1
Variant:
c.106C>A
(p.Leu36Ile)
rsID: rs11557064
Ref Allele: G
Alt Allele: T
Freq: 0.7788%rare
CADD: 22.7
ClinVar Submissions (2)
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Feb 22, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 6:166780349
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Feb 22, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 6:166780349
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
FMN1
Variant:
c.2929G>A
(p.Glu977Lys)
rsID: rs150962800
Ref Allele: C
Alt Allele: T
Freq: 0.7788%rare
CADD: 26.7
ClinVar Submissions (1)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Sep 12, 2017
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 15:33260973
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
AGGF1
Variant:
c.397G>A
(p.Glu133Lys)
rsID: rs34203073
Ref Allele: G
Alt Allele: A
Freq: 0.7788%rare
CADD: 8.512
ClinVar Submissions (1)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Mar 29, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 5:76331449
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Likely benign
Hetero
Gene:
SP110
Variant:
c.376G>A
(p.Gly126Ser)
rsID: rs41309088
Ref Allele: C
Alt Allele: T
Freq: 0.7987%rare
CADD: 9.03
ClinVar Submissions (2)
Hepatic veno-occlusive disease with immunodeficiency (VODI) is characterized by: (1) primary immunodeficiency; and (2) terminal hepatic lobular vascular occlusion and hepatic fibrosis manifest as hepatomegaly and/or hepatic failure. Onset is usually before age six months. The immunodeficiency comprises severe hypogammaglobulinemia, clinical evidence of T-cell immunodeficiency with normal numbers of circulating T cells, absent lymph node germinal centers, and absent tissue plasma cells. Bacterial and opportunistic infections including Pneumocystis jirovecii infection, mucocutaneous candidiasis, and enteroviral or cytomegalovirus infections occur. In the past the prognosis for affected individuals was poor, with 100% mortality in the first year of life if unrecognized and untreated with intravenous immunoglobulin (IVIG) and Pneumocystis jirovecii prophylaxis. However, with early recognition and treatment there is a marked improvement in prognosis.
Last Evaluated: Jul 25, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:231077683
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
REEP1
Variant:
c.*1015G>A
rsID: rs17510310
Ref Allele: C
Alt Allele: T
Freq: 0.8187%rare
CADD: 1.251
ClinVar Submissions (1)
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 2:86443208
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Likely benign
Hetero
Gene:
ZNF407
Variant:
c.181A>G
(p.Ser61Gly)
rsID: rs75994611
Ref Allele: A
Alt Allele: G
Freq: 0.8187%rare
CADD: 2.425
ClinVar Submissions (2)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Feb 16, 2015
Review Status: criteria provided, single submitter
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 18:72343156
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
AP4M1
Variant:
c.1305C>T
(p.Asn435=)
rsID: rs4134932
Ref Allele: C
Alt Allele: T
Freq: 0.9185%rare
CADD: 17.94
ClinVar Submissions (3)
AP-4-associated hereditary spastic paraplegia (HSP), also known as AP-4 deficiency syndrome, is a group of neurodegenerative disorders characterized by a progressive, complex spastic paraplegia with onset typically in infancy or early childhood. Early-onset hypotonia evolves into progressive lower-extremity spasticity. The majority of children become non-ambulatory and usually wheelchair bound. Over time spasticity progresses to involve the upper extremities, resulting in a spastic tetraplegia. Associated complications include dysphagia, contractures, foot deformities, dysregulation of bladder and bowel function, and a pseudobulbar affect. About 50% of affected individuals have seizures. Postnatal microcephaly (usually in the -2SD to -3SD range) is common. All have global developmental delay. Speech development is significantly impaired and many affected individuals remain nonverbal. Intellectual disability in older children is usually moderate to severe.
Last Evaluated: Jul 31, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 7:99704448
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jul 31, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 7:99704448
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
GPR179
Variant:
c.5385C>T
(p.Gly1795=)
rsID: rs72832276
Ref Allele: G
Alt Allele: A
Freq: 0.9585%rare
CADD: 0.321
ClinVar Submissions (1)
Complete congenital stationary night blindness (cCSNB) is a clinically and genetically heterogeneous group of retinal disorders characterized by nonprogressive impairment of night vision, absence of the electroretinogram (ERG) b-wave, and variable degrees of involvement of other visual functions. Individuals with cCSNB and animal models of the disorder have an ERG waveform that lacks the b-wave because of failure to transmit the photoreceptor signal through the retinal depolarizing bipolar cells (summary by Peachey et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of congenital stationary night blindness, see CSNB1A (310500).
Last Evaluated: Jun 28, 2017
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 17:36484067
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Likely benign
Hetero
Below are uncommon mutations (frequency between 1% and 5%) found in ClinVar. The data presented has no guarantees of reporting accuracy. Heterozygous variants are repoted as yellow and homozygous variants as red. A red or yellow variant does not necessarily mean one has or carries a condition or disease. This is for research and educational purposes only.
Gene:
LRBA
Variant:
c.4485C>T
(p.Gly1495=)
rsID: rs11735845
Ref Allele: G
Alt Allele: A
Freq: 1.0982%uncommon
CADD: 7.716
ClinVar Submissions (2)
Common variable immunodeficiency-8 with autoimmunity is an autosomal recessive disorder of immune dysregulation. Affected individuals have early childhood onset of recurrent infections, particularly respiratory infections, and also develop variable autoimmune disorders, including idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and inflammatory bowel disease. The presentation and phenotype are highly variable, even within families (summary by Lopez-Herrera et al., 2012 and Alangari et al., 2012). Immunologic findings are also variable and may include decreased B cells, hypogammaglobulinemia, and deficiency of CD4+ T regulatory (Treg) cells (Charbonnier et al., 2015). For a general description and a discussion of genetic heterogeneity of common variable immunodeficiency, see CVID1 (607594).
Last Evaluated: Jul 31, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 4:151765336
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jul 31, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 4:151765336
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
GP1BA
Variant:
c.774C>T
(p.Asn258=)
rsID: rs6066
Ref Allele: C
Alt Allele: T
Freq: 1.1182%uncommon
CADD: 0.319
ClinVar Submissions (1)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: -
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 17:4836673
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
PLEKHG5
Variant:
c.*27T>C
rsID: rs117494970
Ref Allele: A
Alt Allele: G
Freq: 1.1781%uncommon
CADD: 14.75
ClinVar Submissions (1)
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Uncertain significance
Assembly: GRCh37
Chromosome/Position: 1:6527596
This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Conflicting/Uncertain
Hetero
Gene:
DNAH17
Variant:
c.12854G>A
(p.Arg4285Gln)
rsID: rs35973257
Ref Allele: C
Alt Allele: T
Freq: 1.2181%uncommon
CADD: 24.8
ClinVar Submissions (1)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Mar 29, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 17:76422599
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Likely benign
Hetero
Gene:
BLK
Variant:
c.211G>A
(p.Ala71Thr)
rsID: rs55758736
Ref Allele: G
Alt Allele: A
Freq: 1.238%uncommon
CADD: 13.44
ClinVar Submissions (7)
Maturity-onset diabetes of the young is an autosomal dominant form of diabetes typically occurring before 25 years of age and caused by primary insulin secretion defects. Despite its low prevalence, MODY is not a single entity but represents genetic, metabolic, and clinical heterogeneity (Vaxillaire and Froguel, 2008). Genetic Heterogeneity of MODY MODY1 (125850) is caused by heterozygous mutation in the hepatocyte nuclear factor-4-alpha gene (HNF4A; 600281) on chromosome 20. MODY2 (125851) is caused by heterozygous mutation in the glucokinase gene (GCK; 138079) on chromosome 7. MODY3 (600496) is caused by heterozygous mutation in the hepatocyte nuclear factor-1alpha gene (HNF1A; 142410) on chromosome 12q24.2. MODY4 (606392) is caused by heterozygous mutation in the pancreas/duodenum homeobox protein-1 gene (PDX1; 600733) on chromosome 13q12.1. MODY5 (137920) is caused by heterozygous mutation in the gene encoding hepatic transcription factor-2 (TCF2; 189907) on chromosome 17cen-q21.3. MODY6 (606394) is caused by heterozygous mutation in the NEUROD1 gene (601724) on chromosome 2q32. MODY7 (610508) is caused by heterozygous mutation in the KLF11 gene (603301) on chromosome 2p25. MODY8 (609812), or diabetes-pancreatic exocrine dysfunction syndrome, is caused by heterozygous mutation in the CEL gene (114840) on chromosome 9q34. MODY9 (612225) is caused by heterozygous mutation in the PAX4 gene (167413) on chromosome 7q32. MODY10 (613370) is caused by heterozygous mutation in the insulin gene (INS; 176730) on chromosome 11p15.5. MODY11 (613375) is caused by heterozygous mutation in the BLK gene (191305) on chromosome 8p23. MODY13 (616329) is caused by heterozygous mutation in the KCNJ11 gene (600937) on chromosome 11p15. MODY14 (616511) is caused by heterozygous mutation in the APPL1 gene (604299) on chromosome 3p14.
Last Evaluated: Apr 21, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 7
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 8:11405576
OMIM Allelic Variant: 191305.0001
Last Evaluated: Apr 21, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 7
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 8:11405576
OMIM Allelic Variant: 191305.0001
Diabetes mellitus caused by mutation(s) in a single gene, usually presenting in childhood or early adulthood.
Last Evaluated: Apr 21, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 7
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 8:11405576
OMIM Allelic Variant: 191305.0001
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Apr 21, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 7
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 8:11405576
OMIM Allelic Variant: 191305.0001
This individual has one copy of the genetic mutation, and because the condition(s) are autosomal dominant, they may manifest the condition rather than just being a carrier. This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Clinically Significant Conflicting/Uncertain
Hetero
Gene:
RAD50
Variant:
c.551+85A>G
rsID: rs75639632
Ref Allele: A
Alt Allele: G
Freq: 1.238%uncommon
CADD: 1.96
ClinVar Submissions (2)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterised by growth retardation, short stature, developmental delay, intellectual disability, craniofacial dysmorphism (severe microcephaly, sloping forehead, prominent eyes, broad nasal ridge, hypoplastic nasal septum, epicanthal folds), spontaneous chromosomal instability, cellular hypersensitivity to ionising radiation and radioresistant DNA synthesis, without severe infections, immunodeficiency or cancer predisposition. Additional reported features include mild spasticity, slight and nonprogressive ataxia, hyperopia, multiple pigmented nevi, widely spaced nipples, and clinodactyly.
Last Evaluated: May 25, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 5:131915279
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: May 25, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 5:131915279
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
NPHP1
Variant:
c.115C>A
(p.Pro39Thr)
rsID: rs33958626
Ref Allele: G
Alt Allele: T
Freq: 1.278%uncommon
CADD: 14.38
ClinVar Submissions (6)
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Last Evaluated: Apr 07, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 6
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:110959026
The nephronophthisis (NPH) phenotype is characterized by reduced renal concentrating ability, chronic tubulointerstitial nephritis, cystic renal disease, and progression to end-stage renal disease (ESRD) before age 30 years. Three age-based clinical subtypes are recongnized: infantile, juvenile, and adolescent/adult. Infantile NPH can present in utero with oligohydramnios sequence (limb contractures, pulmonary hypoplasia and facial dysmorphisms) or postnatally with renal manifestations that progress to ESRD before age 3 years. Juvenile NPH, the most prevalent subtype, typically presents with polydipsia and polyuria, growth retardation, chronic iron-resistant anemia, or other findings related to chronic kidney disease (CKD). Hypertension is typically absent due to salt wasting. ESRD develops at a median age of 13 years. Ultrasound findings are increased echogenicity, reduced corticomedullary differentiation, and renal cysts (in 50% of affected individuals). Histologic findings include tubulointerstitial fibrosis, thickened and disrupted tubular basement membrane, sporadic corticomedullary cysts, and normal or reduced kidney size. Adolescent/ adult NPH is clinically similar to juvenile NPH, but ESRD develops at a median age of 19 years. Within a subtype inter- and intrafamilial variability in rate of progression to ESRD is considerable. Approximately 80%-90% of individuals with the NPH phenotype have no extrarenal features (i.e., they have isolated NPH); ~10%-20% have extrarenal manifestations that constitute a recognizable syndrome (e.g., Joubert syndrome, Bardet-Biedl syndrome, Jeune syndrome and related skeletal disorders, Meckel-Gruber syndrome, Senior-Løken syndrome, Leber congenital amaurosis, COACH syndrome, and oculomotor apraxia, Cogan type).
Last Evaluated: Apr 07, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 6
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:110959026
Senior-Loken syndrome is an autosomal recessive disease with the main features of nephronophthisis (NPHP; see 256100) and Leber congenital amaurosis (see 204000). Mutations in some of the same genes that cause nephronophthisis (see 256100) cause Senior-Loken syndrome. Genetic Heterogeneity of Senior-Loken Syndrome Other forms of SLSN include SLSN4 (606996), caused by mutation in the NPHP4 gene (607215) on chromosome 1p36; SLSN5 (609254), caused by mutation in the NPHP5 gene (IQCB1; 609237) on chromosome 3q13; SLSN6 (610189), caused by mutation in the NPHP6 gene (CEP290; 610142) on chromosome 12q21; SLSN7 (613615), caused by mutation in the SDCCAG8 gene (613524) on chromosome 1q43; SLSN8 (616307), caused by mutation in the WDR19 gene (608151) on chromosome 4p14; and SLSN9 (616629), caused by mutation in the TRAF3IP1 gene (607380) on chromosome 2q37. Another form of SLSN, SLSN3 (606995), has been mapped to a locus on chromosome 3q22, overlapping the NPHP3 locus (604387).
Last Evaluated: Apr 07, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 6
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:110959026
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Apr 07, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 6
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:110959026
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
CIDEC
Variant:
c.146C>T
(p.Thr49Met)
rsID: rs61742367
Ref Allele: G
Alt Allele: A
Freq: 1.2979%uncommon
CADD: 17.5
ClinVar Submissions (1)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Nov 06, 2013
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 3:9918811
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
PEX16
Variant:
c.307G>A
(p.Val103Met)
rsID: rs11553094
Ref Allele: C
Alt Allele: T
Freq: 1.3179%uncommon
CADD: 22.5
ClinVar Submissions (2)
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Dec 15, 2015
Review Status: criteria provided, single submitter
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 11:45937306
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Dec 15, 2015
Review Status: criteria provided, single submitter
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 11:45937306
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
JAGN1
Variant:
c.244A>G
(p.Ile82Val)
rsID: rs35365817
Ref Allele: A
Alt Allele: G
Freq: 1.3179%uncommon
CADD: 15.8
ClinVar Submissions (1)
Severe congenital neutropenia is a condition that causes affected individuals to be prone to recurrent infections. People with this condition have a shortage (deficiency) of neutrophils, a type of white blood cell that plays a role in inflammation and in fighting infection. The deficiency of neutrophils, called neutropenia, is apparent at birth or soon afterward. It leads to recurrent infections beginning in infancy, including infections of the sinuses, lungs, and liver. Affected individuals can also develop fevers and inflammation of the gums (gingivitis) and skin. Approximately 40 percent of affected people have decreased bone density (osteopenia) and may develop osteoporosis, a condition that makes bones progressively more brittle and prone to fracture. In people with severe congenital neutropenia, these bone disorders can begin at any time from infancy through adulthood.Approximately 20 percent of people with severe congenital neutropenia develop certain cancerous conditions of the blood, particularly myelodysplastic syndrome or leukemia during adolescence.Some people with severe congenital neutropenia have additional health problems such as seizures, developmental delay, or heart and genital abnormalities.
Last Evaluated: Aug 07, 2017
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 3:9934753
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
FYCO1
Variant:
c.3789A>G
(p.Thr1263=)
rsID: rs41289618
Ref Allele: T
Alt Allele: C
Freq: 1.3578%uncommon
CADD: 2.32
ClinVar Submissions (2)
Mutations in the FYCO1 gene have been identified in families with autosomal recessive cataract described as congenital and congenital nuclear. The preferred title/symbol of this entry was formerly 'Cataract, Autosomal Recessive Congenital 2; CATC2.'
Last Evaluated: Mar 03, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 3:45999910
A congenital cataract.
Last Evaluated: Mar 03, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 3:45999910
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
ETFA
Variant:
c.*268A>G
rsID: rs80292319
Ref Allele: T
Alt Allele: C
Freq: 1.3778%uncommon
CADD: 10.81
ClinVar Submissions (1)
Glutaric aciduria II (GA2) is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It differs from GA I (GA1; 231670) in that multiple acyl-CoA dehydrogenase deficiencies result in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids. GA II results from deficiency of any 1 of 3 molecules: the alpha (ETFA) and beta (ETFB) subunits of electron transfer flavoprotein, and electron transfer flavoprotein dehydrogenase (ETFDH). The clinical picture of GA II due to the different defects appears to be indistinguishable; each defect can lead to a range of mild or severe cases, depending presumably on the location and nature of the intragenic lesion, i.e., mutation, in each case (Goodman, 1993; Olsen et al., 2003). The heterogeneous clinical features of patients with MADD fall into 3 classes: a neonatal-onset form with congenital anomalies (type I), a neonatal-onset form without congenital anomalies (type II), and a late-onset form (type III). The neonatal-onset forms are usually fatal and are characterized by severe nonketotic hypoglycemia, metabolic acidosis, multisystem involvement, and excretion of large amounts of fatty acid- and amino acid-derived metabolites. Symptoms and age at presentation of late-onset MADD are highly variable and characterized by recurrent episodes of lethargy, vomiting, hypoglycemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occurs. The organic aciduria in patients with the late-onset form of MADD is often intermittent and only evident during periods of illness or catabolic stress (summary by Frerman and Goodman, 2001). Importantly, riboflavin treatment has been shown to ameliorate the symptoms and metabolic profiles in many MADD patients, particularly those with type III, the late-onset and mildest form (Liang et al., 2009).
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 15:76508632
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Likely benign
Hetero
Gene:
SPTA1
Variant:
c.2909C>A
(p.Ala970Asp)
rsID: rs35948326
Ref Allele: G
Alt Allele: T
Freq: 1.4177%uncommon
CADD: 22.5
ClinVar Submissions (5)
Last Evaluated: Apr 13, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 5
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 1:158624528
OMIM Allelic Variant: 182860.0009
Last Evaluated: Apr 13, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 5
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 1:158624528
OMIM Allelic Variant: 182860.0009
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Apr 13, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 5
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 1:158624528
OMIM Allelic Variant: 182860.0009
The data does not specify whether the genetic variant is autosomal recessive or autosomal dominant. For a definitive determination, refer to resources such as OMIM. This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Low clinical importance, Uncertain benign — This variant, also called alpha-IIa, has been seen frequently in individuals with recessive Hereditary spherocytosis. This appears to be the result of linkage to alpha-LEPRA (a C>T substitution at position -99 of intron 30); A970D is later reported as functionally neutral.
Clinically Significant Conflicting/Uncertain
Hetero
Gene:
LYRM7
Variant:
c.42G>A
(p.Leu14=)
rsID: rs113642581
Ref Allele: G
Alt Allele: A
Freq: 1.4377%uncommon
CADD: 12.02
ClinVar Submissions (2)
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Feb 22, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 5:130515811
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Feb 22, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 5:130515811
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
ABCC6
Variant:
c.2171G>A
(p.Arg724Lys)
rsID: rs58073789
Ref Allele: C
Alt Allele: T
Freq: 1.4577%uncommon
CADD: 5.62
ClinVar Submissions (1)
Pseudoxanthoma elasticum (PXE) is a systemic disorder that affects the elastic tissue of the skin, the eye, and the cardiovascular and gastrointestinal systems. Individuals most commonly present with papules in the skin and/or with angioid streaks of the retina found on routine eye examination or associated with retinal hemorrhage. Rarely, individuals may present with vascular signs and symptoms, such as gastrointestinal bleeding, angina, or intermittent claudication. The most frequent cause of morbidity and disability in PXE is reduced vision from macular hemorrhage and disciform scarring of the macula. Most affected individuals live a normal life span.
Last Evaluated: -
Review Status: no assertion criteria provided
Number of Submitters: 1
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 16:16276345
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
ZFYVE27
Variant:
c.378G>A
(p.Lys126=)
rsID: rs75060573
Ref Allele: G
Alt Allele: A
Freq: 1.4776%uncommon
CADD: 9.318
ClinVar Submissions (4)
Spasticity and weakness of the leg and hip muscles.
Last Evaluated: Jul 25, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 4
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 10:99504595
Last Evaluated: Jul 25, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 4
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 10:99504595
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jul 25, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 4
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 10:99504595
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
DIS3L2
Variant:
c.1448G>A
(p.Arg483Gln)
rsID: rs148474013
Ref Allele: G
Alt Allele: A
Freq: 1.4976%uncommon
CADD: 26.5
ClinVar Submissions (3)
Perlman syndrome is an autosomal recessive congenital overgrowth syndrome with similarities to Beckwith-Wiedemann syndrome (BWS; 130650). Affected children are large at birth, are hypotonic, and show organomegaly, characteristic facial dysmorphisms (inverted V-shaped upper lip, prominent forehead, deep-set eyes, broad and flat nasal bridge, and low-set ears), renal anomalies (nephromegaly and hydronephrosis), frequent neurodevelopmental delay, and high neonatal mortality. Perlman syndrome is associated with a high risk of Wilms tumor, with a 64% incidence in infants surviving beyond the neonatal period. The tumor is diagnosed at an earlier age in these individuals compared with sporadic cases (less than 2 years and 3-4 years of age, respectively), and there is a high frequency of bilateral tumors (55%). Histologic examination of the kidneys in children with Perlman syndrome shows frequent nephroblastomatosis, which is a precursor lesion for Wilms tumor (summary by Astuti et al., 2012).
Last Evaluated: Aug 11, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:233127939
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Aug 11, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 2:233127939
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
RHO
Variant:
c.*313C>T
rsID: rs55941599
Ref Allele: C
Alt Allele: T
Freq: 1.5375%uncommon
CADD: 14.91
ClinVar Submissions (1)
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 3:129252874
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 3:129252874
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Likely benign
Hetero
Gene:
SPG11
Variant:
c.3420G>A
(p.Leu1140=)
rsID: rs36014111
Ref Allele: C
Alt Allele: T
Freq: 1.5575%uncommon
CADD: 11.17
ClinVar Submissions (7)
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 7
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 15:44900675
Spastic paraplegia 11 (SPG11) is characterized by progressive spasticity and weakness of the lower limbs frequently associated with the following: mild intellectual disability with learning difficulties in childhood and/or progressive cognitive decline; peripheral neuropathy; pseudobulbar involvement; and increased reflexes in the upper limbs. Less frequent findings include: cerebellar signs (ataxia, nystagmus, saccadic pursuit); retinal degeneration; pes cavus; scoliosis; and parkinsonism. Onset occurs mainly during infancy or adolescence (range: age 1-31 years). Most affected individuals become wheelchair bound one or two decades after disease onset.
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 7
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 15:44900675
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 7
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 15:44900675
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
TNK2
Variant:
c.3113G>A
(p.Arg1038His)
rsID: rs13433937
Ref Allele: C
Alt Allele: T
Freq: 1.6174%uncommon
CADD: 22.6
ClinVar Submissions (1)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: -
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 3:195591056
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
NEK1
Variant:
c.1388C>T
(p.Ala463Val)
rsID: rs34540355
Ref Allele: G
Alt Allele: A
Freq: 1.6174%uncommon
CADD: 15.98
ClinVar Submissions (5)
A rare congenital lethal syndrome characterized by the presence of extra fingers and toes and short ribs, the latter resulting in inability of the lungs to expand. The newborn dies shortly after birth.
Last Evaluated: Jun 07, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 5
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 4:170477125
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). For a discussion of genetic heterogeneity of short-rib thoracic dysplasia, see SRTD1 (208500).
Last Evaluated: Jun 07, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 5
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 4:170477125
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jun 07, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 5
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 4:170477125
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
PSMB8
Variant:
c.22G>A
(p.Gly8Arg)
rsID: rs114772012
Ref Allele: C
Alt Allele: T
Freq: 1.6773%uncommon
CADD: 23.8
ClinVar Submissions (2)
This autosomal recessive systemic autoinflammatory disorder is characterized by early childhood onset of annular erythematous plaques on the face and extremities with subsequent development of partial lipodystrophy and laboratory evidence of immune dysregulation. More variable features include recurrent fever, severe joint contractures, muscle weakness and atrophy, hepatosplenomegaly, basal ganglia calcifications, and microcytic anemia (summary by Agarwal et al., 2010; Kitamura et al., 2011; Arima et al., 2011). This disorder encompasses Nakajo-Nishimura syndrome (NKJO); joint contractures, muscular atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome); and chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE). Among Japanese patients, this disorder is best described as Nakajo-Nishimura syndrome, since both Nakajo (1939) and Nishimura et al. (1950) contributed to the original phenotypic descriptions. Genetic Heterogeneity of Proteasome-Associated Autoinflammatory Syndrome See also PRAAS2 (618048), caused by mutation in the POMP gene (613386) on chromosome 13q12, and PRAAS3 (617591), caused by mutation in the PSMB4 gene (602177) on chromosome 1q21.
Last Evaluated: Aug 07, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 6:32811752
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
TSC1
Variant:
c.*107T>C
rsID: rs116917669
Ref Allele: A
Alt Allele: G
Freq: 1.7173%uncommon
CADD: 5.324
ClinVar Submissions (2)
Focal cortical dysplasia type II (FCORD2), or focal cortical dysplasia of Taylor (FCDT), is a cerebral developmental malformation that results in a clinical phenotype of intractable epilepsy, usually requiring surgery. FCORD2 has been classified histologically into 2 subtypes: a type without balloon cells, known as type IIA, and a type with balloon cells, known as type IIB (Palmini et al., 2004). Affected individuals have refractory seizures, usually with onset in early childhood, and may have persistent intellectual disability. Most patients require neurosurgical resection of affected brain tissue to ameliorate seizure frequency and severity (summary by Moller et al., 2016).
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 2
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 9:135771515
Tuberous sclerosis complex (TSC) involves abnormalities of the skin (hypomelanotic macules, confetti skin lesions, facial angiofibromas, shagreen patches, fibrous cephalic plaques, ungual fibromas); brain (subependymal nodules, cortical dysplasias, and subependymal giant cell astrocytomas [SEGAs], seizures, intellectual disability / developmental delay, psychiatric illness); kidney (angiomyolipomas, cysts, renal cell carcinomas); heart (rhabdomyomas, arrhythmias); and lungs (lymphangioleiomyomatosis [LAM], multifocal micronodular pneumonocyte hyperplasia). Central nervous system tumors are the leading cause of morbidity and mortality; renal disease is the second leading cause of early death.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 2
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 9:135771515
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Likely benign
Hetero
Gene:
LIMS2
Variant:
c.261C>T
(p.Tyr87=)
rsID: rs35765118
Ref Allele: G
Alt Allele: A
Freq: 1.7772%uncommon
CADD: 18.88
ClinVar Submissions (2)
Autosomal recessive muscular dystrophy with cardiomyopathy and triangular tongue (MDRCMTT) is an autosomal recessive muscle disorder characterized by onset of severe and progressive muscle weakness and atrophy in childhood, resulting in loss of independent ambulation. Patients may also have dilated cardiomyopathy and have macroglossia with a small tip, resulting in a triangular appearance of the tongue (summary by Warman Chardon et al., 2015).
Last Evaluated: Aug 02, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 2:128412453
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Aug 02, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 2:128412453
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
SLC6A5
Variant:
c.2299G>A
(p.Gly767Arg)
rsID: rs16906628
Ref Allele: G
Alt Allele: A
Freq: 1.8171%uncommon
CADD: 25.4
ClinVar Submissions (1)
Hereditary hyperekplexia (HPX) is characterized by generalized stiffness immediately after birth that normalizes during the first years of life; excessive startle reflex (eye blinking and a flexor spasm of the trunk) to unexpected (particularly auditory) stimuli; and a short period of generalized stiffness following the startle response during which voluntary movements are impossible. Exaggerated head-retraction reflex (HRR) consisting of extension of the head followed by violent flexor spasms of limbs and neck muscles elicited by tapping the tip of the nose is observed in most children. Other findings include periodic limb movements in sleep (PLMS) and hypnagogic (occurring when falling asleep) myoclonus. Sudden infant death (SIDS) has been reported. Intellect is usually normal; mild intellectual disability may occur.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 11:20676319
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
MC1R
Variant:
c.451C>T
(p.Arg151Cys)
rsID: rs1805007
Ref Allele: C
Alt Allele: T
Freq: 1.857%uncommon
CADD: 31
ClinVar Submissions (5)
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 5
Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
Assembly: GRCh37
Chromosome/Position: 16:89986117
OMIM Allelic Variant: 155555.0004
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 5
Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
Assembly: GRCh37
Chromosome/Position: 16:89986117
OMIM Allelic Variant: 155555.0004
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 5
Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
Assembly: GRCh37
Chromosome/Position: 16:89986117
OMIM Allelic Variant: 155555.0004
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 5
Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
Assembly: GRCh37
Chromosome/Position: 16:89986117
OMIM Allelic Variant: 155555.0004
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 5
Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
Assembly: GRCh37
Chromosome/Position: 16:89986117
OMIM Allelic Variant: 155555.0004
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 5
Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
Assembly: GRCh37
Chromosome/Position: 16:89986117
OMIM Allelic Variant: 155555.0004
Last Evaluated: Aug 04, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 5
Clinical Significance: Conflicting interpretations of pathogenicity, Affects, association, risk factor
Assembly: GRCh37
Chromosome/Position: 16:89986117
OMIM Allelic Variant: 155555.0004
The data does not specify whether the genetic variant is autosomal recessive or autosomal dominant. For a definitive determination, refer to resources such as OMIM. This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Insufficiently evaluated benign — The MC1R gene encodes for a receptor protein for a melanin-stimulating hormone, so it is involved in melanogenesis (melanin production). Polymorphisms of this gene have been shown to cause increased susceptibility of skin cells to UV damage. Arg151Cys has been associated with melanoma.
Clinically Significant Conflicting/Uncertain
Hetero
Gene:
TNPO3
Variant:
c.321+16C>T
rsID: rs17424179
Ref Allele: G
Alt Allele: A
Freq: 1.9369%uncommon
CADD: 14.83
ClinVar Submissions (2)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jan 19, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 7:128657995
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
CPLANE1
Variant:
c.3743G>A
(p.Gly1248Asp)
rsID: rs72736758
Ref Allele: C
Alt Allele: T
Freq: 1.9369%uncommon
CADD: 23.3
ClinVar Submissions (7)
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Last Evaluated: Jul 11, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 7
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 5:37196028
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Last Evaluated: Jul 11, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 7
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 5:37196028
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Last Evaluated: Jul 11, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 7
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 5:37196028
Orofaciodigital syndrome type VI (OFD6), or Varadi syndrome, is a rare autosomal recessive disorder distinguished from other orofaciodigital syndromes by metacarpal abnormalities with central polydactyly and by cerebellar abnormalities, including the molar tooth sign (summary by Doss et al., 1998 and Lopez et al., 2014).
Last Evaluated: Jul 11, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 7
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 5:37196028
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jul 11, 2017
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 7
Clinical Significance: Conflicting interpretations of pathogenicity
Assembly: GRCh37
Chromosome/Position: 5:37196028
This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Conflicting/Uncertain
Hetero
Gene:
LCT
Variant:
c.*429A>C
rsID: rs77631953
Ref Allele: T
Alt Allele: G
Freq: 1.9768%uncommon
CADD: 4.586
ClinVar Submissions (1)
Congenital lactase deficiency is a severe gastrointestinal disorder characterized by watery diarrhea in infants fed with breast milk or other lactose-containing formulas.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 2:136545465
An inability to digest lactose.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 2:136545465
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Likely benign
Hetero
Gene:
BRD2
Variant:
c.1330-4G>C
rsID: rs3097644
Ref Allele: C
Alt Allele: G
Freq: 2.0168%uncommon
CADD: 5.864
ClinVar Submissions (1)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jul 03, 2013
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 6:32945530
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
MYH3
Variant:
c.6T>C
(p.Ser2=)
rsID: rs17817203
Ref Allele: A
Alt Allele: G
Freq: 2.0967%uncommon
CADD: 6.89
ClinVar Submissions (3)
A non-progressive finding characterized by multiple joint contractures found throughout the body at birth.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 17:10558376
Freeman-Sheldon syndrome (FSS), or DA2A, is phenotypically similar to DA1. In addition to contractures of the hands and feet, FSS is characterized by oropharyngeal abnormalities, scoliosis, and a distinctive face that includes a very small oral orifice (often only a few millimeters in diameter at birth), puckered lips, and an H-shaped dimple of the chin; hence, FSS has been called 'whistling face syndrome.' The limb phenotypes of DA1 and FSS may be so similar that they can only be distinguished by the differences in facial morphology (summary by Bamshad et al., 2009). For a general phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1 (108120).
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 17:10558376
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 17:10558376
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
COL1A1
Variant:
c.3223G=
(p.Ala1075=)
rsID: rs1800215
Ref Allele: C
Freq: 2.1166%uncommon
CADD: 16.77
ClinVar Submissions (1)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Dec 14, 2015
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 17:48265495
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
MYH3
Variant:
c.3008C>T
(p.Ala1003Val)
rsID: rs34088014
Ref Allele: G
Alt Allele: A
Freq: 2.1765%uncommon
CADD: 23.2
ClinVar Submissions (3)
A non-progressive finding characterized by multiple joint contractures found throughout the body at birth.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 17:10542709
Freeman-Sheldon syndrome (FSS), or DA2A, is phenotypically similar to DA1. In addition to contractures of the hands and feet, FSS is characterized by oropharyngeal abnormalities, scoliosis, and a distinctive face that includes a very small oral orifice (often only a few millimeters in diameter at birth), puckered lips, and an H-shaped dimple of the chin; hence, FSS has been called 'whistling face syndrome.' The limb phenotypes of DA1 and FSS may be so similar that they can only be distinguished by the differences in facial morphology (summary by Bamshad et al., 2009). For a general phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1 (108120).
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 17:10542709
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 17:10542709
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
MYH3
Variant:
c.5254G>A
(p.Ala1752Thr)
rsID: rs34393601
Ref Allele: C
Alt Allele: T
Freq: 2.1765%uncommon
CADD: 24.5
ClinVar Submissions (3)
A non-progressive finding characterized by multiple joint contractures found throughout the body at birth.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 17:10534960
Freeman-Sheldon syndrome (FSS), or DA2A, is phenotypically similar to DA1. In addition to contractures of the hands and feet, FSS is characterized by oropharyngeal abnormalities, scoliosis, and a distinctive face that includes a very small oral orifice (often only a few millimeters in diameter at birth), puckered lips, and an H-shaped dimple of the chin; hence, FSS has been called 'whistling face syndrome.' The limb phenotypes of DA1 and FSS may be so similar that they can only be distinguished by the differences in facial morphology (summary by Bamshad et al., 2009). For a general phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1 (108120).
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 17:10534960
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 17:10534960
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
DNAAF4
Variant:
c.271G>A
(p.Val91Ile)
rsID: rs17819126
Ref Allele: C
Alt Allele: T
Freq: 2.1965%uncommon
CADD: 21.5
ClinVar Submissions (1)
Primary ciliary dyskinesia (PCD) is associated with situs abnormalities, abnormal sperm motility, and abnormal ciliary structure and function that result in retention of mucus and bacteria in the respiratory tract leading to chronic otosinopulmonary disease. More than 75% of full-term neonates with PCD have "neonatal respiratory distress" requiring supplemental oxygen for days to weeks. Chronic airway infection, apparent in early childhood, results in bronchiectasis that is almost uniformly present in adulthood. Nasal congestion and sinus infections, apparent in early childhood, persist through adulthood. Chronic/recurrent ear infection, apparent in most young children, can be associated with transient or later irreversible hearing loss. Situs inversus totalis (mirror-image reversal of all visceral organs with no apparent physiologic consequences) is present in 40%-50% of individuals with PCD; heterotaxy (discordance of right and left patterns of ordinarily asymmetric structures that can be associated with significant malformations) is present in approximately 12%. Virtually all males with PCD are infertile as a result of abnormal sperm motility.
Last Evaluated: Aug 12, 2017
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 15:55789910
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
ABCC6
Variant:
c.2224A>G
(p.Ile742Val)
rsID: rs59593133
Ref Allele: T
Alt Allele: C
Freq: 2.2963%uncommon
CADD: 4.019
ClinVar Submissions (1)
Pseudoxanthoma elasticum (PXE) is a systemic disorder that affects the elastic tissue of the skin, the eye, and the cardiovascular and gastrointestinal systems. Individuals most commonly present with papules in the skin and/or with angioid streaks of the retina found on routine eye examination or associated with retinal hemorrhage. Rarely, individuals may present with vascular signs and symptoms, such as gastrointestinal bleeding, angina, or intermittent claudication. The most frequent cause of morbidity and disability in PXE is reduced vision from macular hemorrhage and disciform scarring of the macula. Most affected individuals live a normal life span.
Last Evaluated: -
Review Status: no assertion criteria provided
Number of Submitters: 1
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 16:16276292
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
ANK3
Variant:
c.402T>C
(p.Asn134=)
rsID: rs1031688
Ref Allele: A
Alt Allele: G
Freq: 2.3962%uncommon
CADD: 10.36
ClinVar Submissions (1)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: -
Review Status: no assertion criteria provided
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 10:62038544
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Likely benign
Homo
Gene:
TSHZ1
Variant:
c.1402G>A
(p.Ala468Thr)
rsID: rs33930274
Ref Allele: G
Alt Allele: A
Freq: 2.6158%uncommon
CADD: 0.001
ClinVar Submissions (1)
Altmann (1955) was the first to describe a congenital aural atresia (CAA) classification, which has been modified over the years (Cremers et al., 1988; Schuknecht, 1989; Jahrsdoerfer et al., 1992). In CAA type I, there is bony or fibrous atresia of the lateral part of the external auditory canal and an almost normal medial part and middle ear. CAA type II is the most frequent type and is characterized by partial or total aplasia of the external auditory canal. CAA type IIA involves an external auditory canal with either complete bony atresia of the medial part or partial aplasia that ends blindly in a fistula leading to a rudimentary tympanic membrane. CAA type IIB is characterized by bony stenosis of the total length of the external auditory canal. CAA type III involves bony atresia of the external auditory canal and a very small or absent middle-ear cavity (summary by Feenstra et al., 2011).
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 18:72998899
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
SYNE2
Variant:
c.7690A>G
(p.Ile2564Val)
rsID: rs11628107
Ref Allele: A
Alt Allele: G
Freq: 2.9153%uncommon
CADD: 9.6
ClinVar Submissions (5)
Emery-Dreifuss muscular dystrophy (EDMD) is characterized by the clinical triad of joint contractures that begin in early childhood, slowly progressive muscle weakness and wasting initially in a humero-peroneal distribution that later extends to the scapular and pelvic girdle muscles, and cardiac involvement that may manifest as palpitations, presyncope and syncope, poor exercise tolerance, and congestive heart failure. Age of onset, severity, and progression of muscle and cardiac involvement demonstrate both inter- and intrafamilial variability. Clinical variability ranges from early onset with severe presentation in childhood to late onset with slow progression in adulthood. In general, joint contractures appear during the first two decades, followed by muscle weakness and wasting. Cardiac involvement usually occurs after the second decade.
Last Evaluated: Aug 02, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 5
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 14:64518321
Last Evaluated: Aug 02, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 5
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 14:64518321
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Aug 02, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 5
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 14:64518321
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
RP1L1
Variant:
c.5447G>A
(p.Gly1816Asp)
rsID: rs79019225
Ref Allele: C
Alt Allele: T
Freq: 3.0152%uncommon
CADD: 2.693
ClinVar Submissions (1)
Occult macular dystrophy is characterized by progressive decline of visual acuity in both eyes, associated with a normal fundus and normal fluorescein angiography. Patients have normal full-field electroretinograms (ERGs) but severely reduced focal macular ERGs, as recorded by conventional techniques using small stimuli under background illumination. OCMD patients are believed to have localized retinal dysfunction distal to the ganglion cells in the central retina (summary by Piao et al., 2000).
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 8:10466161
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Likely benign
Hetero
Gene:
LAMB2
Variant:
c.2740G>A
(p.Gly914Arg)
rsID: rs35713889
Ref Allele: C
Alt Allele: T
Freq: 3.0551%uncommon
CADD: 32
ClinVar Submissions (5)
A collection of symptoms that include severe edema, proteinuria, and hypoalbuminemia; it is indicative of renal dysfunction.
Last Evaluated: Nov 02, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 5
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 3:49162583
Nephrotic syndrome type 5 is an autosomal recessive disorder characterized by very early onset of progressive renal failure manifest as proteinuria with consecutive edema starting in utero or within the first 3 months of life. A subset of patients may develop mild ocular anomalies, such as myopia, nystagmus, and strabismus (summary by Hasselbacher et al., 2006). Mutation in the LAMB2 gene can also cause Pierson syndrome (609049), which is characterized by nephrotic syndrome, distinct ocular anomalies, namely microcoria, and neurodevelopmental delay. For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).
Last Evaluated: Nov 02, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 5
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 3:49162583
Pierson syndrome is an autosomal recessive disorder comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct ocular abnormalities, including microcoria and hypoplasia of the ciliary and pupillary muscles, as well as other anomalies. Many patients die early, and those who survive tend to show neurodevelopmental delay and visual loss (summary by Zenker et al., 2004). Mutations in the LAMB2 gene also cause nephrotic syndrome type 5 with or without mild ocular anomalies (NPHS5; 614199).
Last Evaluated: Nov 02, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 5
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 3:49162583
Pierson syndrome is an autosomal recessive disorder comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct ocular abnormalities, including microcoria and hypoplasia of the ciliary and pupillary muscles, as well as other anomalies. Many patients die early, and those who survive tend to show neurodevelopmental delay and visual loss (summary by Zenker et al., 2004). Mutations in the LAMB2 gene also cause nephrotic syndrome type 5 with or without mild ocular anomalies (NPHS5; 614199).
Last Evaluated: Nov 02, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 5
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 3:49162583
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Nov 02, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 5
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 3:49162583
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Nov 02, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 5
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 3:49162583
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
ARSA
Variant:
c.*1746G>A
rsID: rs73172277
Ref Allele: C
Alt Allele: T
Freq: 3.0551%uncommon
CADD: 0.295
ClinVar Submissions (1)
Arylsulfatase A deficiency (also known as metachromatic leukodystrophy or MLD) is characterized by three clinical subtypes: late-infantile MLD, juvenile MLD, and adult MLD. Age of onset within a family is usually similar. The disease course may be from several years in the late-infantile-onset form to decades in the juvenile- and adult-onset forms. Late-infantile MLD. Onset is before age 30 months. Typical presenting findings include weakness, hypotonia, clumsiness, frequent falls, toe walking, and dysarthria. As the disease progresses, language, cognitive, and gross and fine motor skills regress. Later signs include spasticity, pain, seizures, and compromised vision and hearing. In the final stages, children have tonic spasms, decerebrate posturing, and general unawareness of their surroundings. Juvenile MLD. Onset is between age 30 months and 16 years. Initial manifestations include decline in school performance and emergence of behavioral problems, followed by gait disturbances. Progression is similar to but slower than in the late-infantile form. Adult MLD. Onset occurs after age 16 years, sometimes not until the fourth or fifth decade. Initial signs can include problems in school or job performance, personality changes, emotional lability, or psychosis; in others, neurologic symptoms (weakness and loss of coordination progressing to spasticity and incontinence) or seizures initially predominate. Peripheral neuropathy is common. Disease course is variable – with periods of stability interspersed with periods of decline – and may extend over two to three decades. The final stage is similar to earlier-onset forms.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Likely benign
Assembly: GRCh37
Chromosome/Position: 22:51061827
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Likely benign
Hetero
Gene:
SLC52A3
Variant:
c.222C>G
(p.Ile74Met)
rsID: rs35655964
Ref Allele: G
Alt Allele: C
Freq: 3.0751%uncommon
CADD: 21.6
ClinVar Submissions (2)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Aug 23, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 20:746197
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
IL17F
Variant:
c.377A>G
(p.Glu126Gly)
rsID: rs2397084
Ref Allele: T
Alt Allele: C
Freq: 3.3147%uncommon
CADD: 28.2
ClinVar Submissions (2)
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 6:52101844
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 2
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 6:52101844
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
SPTB
Variant:
c.4818C>T
(p.Tyr1606=)
rsID: rs4899145
Ref Allele: G
Alt Allele: A
Freq: 3.3147%uncommon
CADD: 0.92
ClinVar Submissions (3)
A peripheral blood finding in which a large number of erythrocytes are shaped in a slightly oval-shaped form.
Last Evaluated: Apr 13, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 14:65241867
Last Evaluated: Apr 13, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 14:65241867
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Apr 13, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 14:65241867
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
TSEN54
Variant:
c.1447C>G
(p.Pro483Ala)
rsID: rs62088470
Ref Allele: C
Alt Allele: G
Freq: 3.4345%uncommon
CADD: 28.4
ClinVar Submissions (4)
Pontocerebellar hypoplasia is a group of related conditions that affect the development of the brain. The term "pontocerebellar" refers to the pons and the cerebellum, which are the brain structures that are most severely affected in many forms of this disorder. The pons is located at the base of the brain in an area called the brainstem, where it transmits signals between the cerebellum and the rest of the brain. The cerebellum, which is located at the back of the brain, normally coordinates movement. The term "hypoplasia" refers to the underdevelopment of these brain regions.Pontocerebellar hypoplasia also causes impaired growth of other parts of the brain, leading to an unusually small head size (microcephaly). This microcephaly is usually not apparent at birth but becomes noticeable as brain growth continues to be slow in infancy and early childhood.Researchers have described at least ten types of pontocerebellar hypoplasia. All forms of this condition are characterized by impaired brain development, delayed development overall, problems with movement, and intellectual disability. The brain abnormalities are usually present at birth, and in some cases they can be detected before birth. Many children with pontocerebellar hypoplasia live only into infancy or childhood, although some affected individuals have lived into adulthood.The two major forms of pontocerebellar hypoplasia are designated as type 1 (PCH1) and type 2 (PCH2). In addition to the brain abnormalities described above, PCH1 causes problems with muscle movement resulting from a loss of specialized nerve cells called motor neurons in the spinal cord, similar to another genetic disorder known as spinal muscular atrophy. Individuals with PCH1 also have very weak muscle tone (hypotonia), joint deformities called contractures, vision impairment, and breathing and feeding problems that are evident from early infancy.Common features of PCH2 include a lack of voluntary motor skills (such as grasping objects, sitting, or walking), problems with swallowing (dysphagia), and an absence of communication, including speech. Affected children typically develop temporary jitteriness (generalized clonus) in early infancy, abnormal patterns of movement described as chorea or dystonia, and stiffness (spasticity). Many also have impaired vision and seizures.The other forms of pontocerebellar hypoplasia, designated as type 3 (PCH3) through type 10 (PCH10), appear to be rare and have each been reported in only a small number of individuals. Because the different types have overlapping features, and some are caused by mutations in the same genes, researchers have proposed that the types be considered as a spectrum instead of distinct conditions.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 4
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 17:73520359
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 4
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 17:73520359
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
TNNI3;TNNT1
Variant:
c.35A>G
(p.Glu12Gly)
rsID: rs112562759
Ref Allele: T
Alt Allele: C
Freq: 3.5943%uncommon
CADD: 20.7
ClinVar Submissions (7)
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 7
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 19:55658387
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 7
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 19:55658387
Familial restrictive cardiomyopathy is a genetic form of heart disease. For the heart to beat normally, the heart (cardiac) muscle must contract and relax in a coordinated way. Oxygen-rich blood from the lungs travels first through the upper chambers of the heart (the atria), and then to the lower chambers of the heart (the ventricles).In people with familial restrictive cardiomyopathy, the heart muscle is stiff and cannot fully relax after each contraction. Impaired muscle relaxation causes blood to back up in the atria and lungs, which reduces the amount of blood in the ventricles.Familial restrictive cardiomyopathy can appear anytime from childhood to adulthood. The first signs and symptoms of this condition in children are failure to gain weight and grow at the expected rate (failure to thrive), extreme tiredness (fatigue), and fainting. Children who are severely affected may also have abnormal swelling or puffiness (edema), increased blood pressure, an enlarged liver, an abnormal buildup of fluid in the abdominal cavity (ascites), and lung congestion. Some children with familial restrictive cardiomyopathy do not have any obvious signs or symptoms, but they may die suddenly due to heart failure. Without treatment, the majority of affected children survive only a few years after they are diagnosed.Adults with familial restrictive cardiomyopathy typically first develop shortness of breath, fatigue, and a reduced ability to exercise. Some individuals have an irregular heart beat (arrhythmia) and may also experience a sensation of fluttering or pounding in the chest (palpitations) and dizziness. Abnormal blood clots are commonly seen in adults with this condition. Without treatment, approximately one-third of adults with familial restrictive cardiomyopathy do not survive more than five years after diagnosis.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 7
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 19:55658387
A condition in which the myocardium is hypertrophied without an obvious cause. The hypertrophy is generally asymmetric and may be associated with obstruction of the ventricular outflow tract.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 7
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 19:55658387
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 7
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 19:55658387
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jun 14, 2016
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 7
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 19:55658387
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
SHROOM3
Variant:
c.4289G>A
(p.Arg1430Gln)
rsID: rs61741104
Ref Allele: G
Alt Allele: A
Freq: 3.6741%uncommon
CADD: 8.809
ClinVar Submissions (1)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Mar 29, 2016
Review Status: criteria provided, single submitter
Number of Submitters: 1
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 4:77675925
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Homo
Gene:
DNAH11
Variant:
c.1199C>T
(p.Thr400Ile)
rsID: rs72655982
Ref Allele: C
Alt Allele: T
Freq: 3.754%uncommon
CADD: 0.006
ClinVar Submissions (4)
Primary ciliary dyskinesia (PCD) is associated with situs abnormalities, abnormal sperm motility, and abnormal ciliary structure and function that result in retention of mucus and bacteria in the respiratory tract leading to chronic otosinopulmonary disease. More than 75% of full-term neonates with PCD have "neonatal respiratory distress" requiring supplemental oxygen for days to weeks. Chronic airway infection, apparent in early childhood, results in bronchiectasis that is almost uniformly present in adulthood. Nasal congestion and sinus infections, apparent in early childhood, persist through adulthood. Chronic/recurrent ear infection, apparent in most young children, can be associated with transient or later irreversible hearing loss. Situs inversus totalis (mirror-image reversal of all visceral organs with no apparent physiologic consequences) is present in 40%-50% of individuals with PCD; heterotaxy (discordance of right and left patterns of ordinarily asymmetric structures that can be associated with significant malformations) is present in approximately 12%. Virtually all males with PCD are infertile as a result of abnormal sperm motility.
Last Evaluated: Jan 24, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 4
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 7:21609691
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jan 24, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 4
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 7:21609691
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
DNAH11
Variant:
c.1702G>A
(p.Ala568Thr)
rsID: rs72655988
Ref Allele: G
Alt Allele: A
Freq: 3.7939%uncommon
CADD: 23
ClinVar Submissions (4)
Primary ciliary dyskinesia (PCD) is associated with situs abnormalities, abnormal sperm motility, and abnormal ciliary structure and function that result in retention of mucus and bacteria in the respiratory tract leading to chronic otosinopulmonary disease. More than 75% of full-term neonates with PCD have "neonatal respiratory distress" requiring supplemental oxygen for days to weeks. Chronic airway infection, apparent in early childhood, results in bronchiectasis that is almost uniformly present in adulthood. Nasal congestion and sinus infections, apparent in early childhood, persist through adulthood. Chronic/recurrent ear infection, apparent in most young children, can be associated with transient or later irreversible hearing loss. Situs inversus totalis (mirror-image reversal of all visceral organs with no apparent physiologic consequences) is present in 40%-50% of individuals with PCD; heterotaxy (discordance of right and left patterns of ordinarily asymmetric structures that can be associated with significant malformations) is present in approximately 12%. Virtually all males with PCD are infertile as a result of abnormal sperm motility.
Last Evaluated: Aug 14, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 4
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 7:21621631
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Aug 14, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 4
Clinical Significance: Benign/Likely benign
Assembly: GRCh37
Chromosome/Position: 7:21621631
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign/Likely benign
Hetero
Gene:
AMPD1
Variant:
c.133C>T
(p.Gln45Ter)
rsID: rs17602729
Ref Allele: G
Alt Allele: A
Freq: 3.8139%uncommon
CADD: 36
ClinVar Submissions (6)
Myoadenylate deaminase deficiency (MMDD) is an autosomal recessive condition that can manifest as exercise-induced muscle pain, occasionally associated with rhabdomyolysis and/or increased serum creatine kinase, or even infantile hypotonia. However, the finding of homozygous mutations among asymptomatic individuals have suggested to some (e.g., Verzijl et al., 1998) that AMPD1 deficiency may be a harmless entity (summary by Castro-Gago et al., 2011). Genetta et al. (2001) stated that AMPD1 deficiency is the most prevalent genetic disease in humans, the number of people heterozygous approaching 10% of Caucasians and individuals of African descent (Sabina et al., 1989). A small percentage of homozygous-deficient individuals, approximately 1.8% of the population, display symptoms of chronic fatigue and lost productivity as well as a predisposition to stress-related ailments, including heart disease and stroke, according to Genetta et al. (2001).
Last Evaluated: Jun 27, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 6
Clinical Significance: Conflicting interpretations of pathogenicity, other
Assembly: GRCh37
Chromosome/Position: 1:115236057
OMIM Allelic Variant: 102770.0001
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Last Evaluated: Jun 27, 2018
Review Status: criteria provided, conflicting interpretations
Number of Submitters: 6
Clinical Significance: Conflicting interpretations of pathogenicity, other
Assembly: GRCh37
Chromosome/Position: 1:115236057
OMIM Allelic Variant: 102770.0001
The individual has two copies of the variant, which suggests they may manifest the associated condition or trait. This variant has conflicting interpretations of pathogenicity and should be interpreted with caution.
Low clinical importance, Likely pathogenic — Causes Adenosine Deaminase Deficiency in a recessive manner. Most of the time individuals do not report symptoms, but when symptoms do exist they to be post-exercise symptoms of muscle weakness, muscle pain, and getting tired more quickly.
Expert Reviewed Clinically Significant Conflicting/Uncertain
Homo
Gene:
NEBL
Variant:
c.1132G>C
(p.Asp378His)
rsID: rs41277370
Ref Allele: C
Alt Allele: G
Freq: 3.8538%uncommon
CADD: 24
ClinVar Submissions (3)
Last Evaluated: Jan 17, 2014
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 10:21134282
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: Jan 17, 2014
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 10:21134282
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
LOXHD1
Variant:
c.1087G>A
(p.Val363Ile)
rsID: rs10163657
Ref Allele: C
Alt Allele: T
Freq: 4.2732%uncommon
CADD: 18.46
ClinVar Submissions (3)
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: May 09, 2017
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 18:44181227
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
TECPR2
Variant:
c.1315C>T
(p.Pro439Ser)
rsID: rs2273906
Ref Allele: C
Alt Allele: T
Freq: 4.2931%uncommon
CADD: 16.97
ClinVar Submissions (3)
SPG49 is an autosomal recessive complicated form of spastic paraplegia, a neurodegenerative disorder of the corticospinal tracts. It is characterized by delayed psychomotor development, mental retardation, and onset of spastic paraplegia in the first decade. Affected individuals also have dysmorphic features, thin corpus callosum on brain imaging, and episodes of central apnea, which may be fatal (summary by Oz-Levi et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800.
Last Evaluated: May 31, 2018
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 14:102898363
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Last Evaluated: May 31, 2018
Review Status: criteria provided, multiple submitters, no conflicts
Number of Submitters: 3
Clinical Significance: Benign
Assembly: GRCh37
Chromosome/Position: 14:102898363
This variant has been classified as benign. Any further interpretation or conclusions drawn should be approached with caution.
Benign
Hetero
Gene:
MUC5B
Variant:
c.-3133G>T
rsID: rs35705950
Ref Allele: G
Alt Allele: T
Freq: 4.6725%uncommon
CADD: 11.96
ClinVar Submissions (2)
Last Evaluated: Jan 28, 2015
Review Status: no assertion criteria provided
Number of Submitters: 2
Clinical Significance: risk factor
Assembly: GRCh37
Chromosome/Position: 11:1241221
OMIM Allelic Variant: 600770.0001
Last Evaluated: Jan 28, 2015
Review Status: no assertion criteria provided
Number of Submitters: 2
Clinical Significance: risk factor
Assembly: GRCh37
Chromosome/Position: 11:1241221
OMIM Allelic Variant: 600770.0001
Hetero