ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.172T>G (p.Phe58Val)

gnomAD frequency: 0.00061  dbSNP: rs138749562
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000150527 SCV000197734 uncertain significance not specified 2014-07-16 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Phe58Val varian t in DSC2 has been reported in 1 individual with DCM (Elliot 2010) and in 1/1254 control chromosomes (Kapplinger 2011). This variant has also been identified in 0.16% (7/4406) of African American chromosomes by the NHLBI Exome Sequencing Pr oject (http://evs.gs.washington.edu/EVS/; dbSNP rs138749562). Phenylalanine (Phe ) at position 58 is not conserved in evolution and 2 mammals (rabbit, pika) carr y a valine (Val) at this position, suggesting that this change may be tolerated. In summary, while the clinical significance of the Phe58Val variant is uncertai n, these data suggest that it is more likely to be benign.
Eurofins Ntd Llc (ga) RCV000725685 SCV000338592 uncertain significance not provided 2016-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000725685 SCV000512857 likely benign not provided 2021-05-19 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 25351510, 20716751, 21636032)
Labcorp Genetics (formerly Invitae), Labcorp RCV001083970 SCV000561706 likely benign Arrhythmogenic right ventricular dysplasia 11 2025-01-23 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000150527 SCV000747971 likely benign not specified 2017-02-28 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001177334 SCV001341529 likely benign Cardiomyopathy 2019-04-01 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001177334 SCV002043568 benign Cardiomyopathy 2019-12-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV002408665 SCV002716718 likely benign Cardiovascular phenotype 2018-12-05 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000150527 SCV004099534 likely benign not specified 2025-01-27 criteria provided, single submitter clinical testing Variant summary: DSC2 c.172T>G (p.Phe58Val) results in a non-conservative amino acid change located in the Cadherin prodomain (IPR014868) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00013 in 250736 control chromosomes, predominantly at a frequency of 0.0019 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 11.69 fold of the estimated maximal expected allele frequency for a pathogenic variant in DSC2 causing Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy phenotype (0.00016). To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 163193). Based on the evidence outlined above, the variant was classified as likely benign.
All of Us Research Program, National Institutes of Health RCV003998188 SCV004819371 likely benign Familial isolated arrhythmogenic right ventricular dysplasia 2024-08-06 criteria provided, single submitter clinical testing
Clinical Genetics, Academic Medical Center RCV000725685 SCV001918078 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000725685 SCV001932955 likely benign not provided no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV003907419 SCV004724003 likely benign DSC2-related disorder 2022-06-02 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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