Submissions for variant NM_024422.6(DSC2):c.2471C>T (p.Ser824Leu)

gnomAD frequency: 0.00016  dbSNP: rs143413607

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000148469	SCV000297176	uncertain significance	Arrhythmogenic right ventricular cardiomyopathy	2015-11-30	criteria provided, single submitter	clinical testing
Invitae	RCV000456802	SCV000551494	likely benign	Arrhythmogenic right ventricular dysplasia 11	2024-01-29	criteria provided, single submitter	clinical testing
Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University	RCV000456802	SCV000891612	uncertain significance	Arrhythmogenic right ventricular dysplasia 11	2017-12-30	criteria provided, single submitter	curation
Color Diagnostics, LLC DBA Color Health	RCV001180330	SCV001345234	uncertain significance	Cardiomyopathy	2023-05-01	criteria provided, single submitter	clinical testing	This missense variant replaces serine with leucine at codon 824 of the DSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in two individuals affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 20864495, 24832006). This variant was also detected in a post-mortem heart tissue sample from an individual with clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy (PMID: 24832006). This variant has also been identified in 29/282414 chromosomes (18/24954 African chromosomes) in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV002444604	SCV002735593	benign	Cardiovascular phenotype	2023-04-18	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
All of Us Research Program, National Institutes of Health	RCV003998167	SCV004816044	uncertain significance	Familial isolated arrhythmogenic right ventricular dysplasia	2024-02-05	criteria provided, single submitter	clinical testing	This missense variant replaces serine with leucine at codon 824 of the DSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in two individuals affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 20864495, 24832006). This variant was also detected in a post-mortem heart tissue sample from an individual with clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy (PMID: 24832006). This variant has also been identified in 29/282414 chromosomes (18/24954 African chromosomes) in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
CSER _CC_NCGL, University of Washington	RCV000148469	SCV000190169	uncertain significance	Arrhythmogenic right ventricular cardiomyopathy	2014-06-01	no assertion criteria provided	research