Total submissions: 13
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular 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 |
RCV000725685 | SCV000338592 | uncertain significance | not provided | 2016-02-08 | criteria provided, single submitter | clinical testing | |
Gene |
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 |
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, |
RCV000150527 | SCV000747971 | likely benign | not specified | 2017-02-28 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV001177334 | SCV001341529 | likely benign | Cardiomyopathy | 2019-04-01 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
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, |
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, |
RCV003998188 | SCV004819371 | likely benign | Familial isolated arrhythmogenic right ventricular dysplasia | 2024-08-06 | criteria provided, single submitter | clinical testing | |
Clinical Genetics, |
RCV000725685 | SCV001918078 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000725685 | SCV001932955 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Prevention |
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). |