ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.2368C>T (p.His790Tyr) (rs114544564)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000154627 SCV000204301 likely benign not specified 2014-05-28 criteria provided, single submitter clinical testing His790Tyr in exon 15 of DSG2: This variant is not expected to have clinical sign ificance because it has been identified in 0.4% (15/3672) of African American ch romosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/E VS/; dbSNP rs114544564).
GeneDx RCV000154627 SCV000512869 likely benign not specified 2017-10-02 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV001086616 SCV000561393 likely benign Arrhythmogenic right ventricular cardiomyopathy, type 10 2020-12-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000618561 SCV000734908 likely benign Cardiovascular phenotype 2018-09-28 criteria provided, single submitter clinical testing Other strong data supporting benign classification
Color Health, Inc RCV000771841 SCV000904555 likely benign Cardiomyopathy 2018-10-29 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000845294 SCV000987325 likely benign not provided 2016-12-22 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001086616 SCV001283591 likely benign Arrhythmogenic right ventricular cardiomyopathy, type 10 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000154627 SCV001437287 likely benign not specified 2020-09-08 criteria provided, single submitter clinical testing Variant summary: DSG2 c.2368C>T (p.His790Tyr) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00036 in 283014 control chromosomes, predominantly at a frequency of 0.0038 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 380 fold of the estimated maximal expected allele frequency for a pathogenic variant in DSG2 causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.2368C>T in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. Six ClinVar submitters (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

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