Submissions for variant NM_001927.4(DES):c.785A>T (p.Glu262Val)

gnomAD frequency: 0.00083  dbSNP: rs147327878

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037252	SCV000060909	uncertain significance	not specified	2016-08-14	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Glu262Val var iant in DES has been identified by our laboratory in 3 African American individu als with features of DCM but is also present in 0.2% (25/10192) of African chrom osomes in the Exome Aggregation Consortium database (ExAC, http://exac.broadinst itute.org; dbSNP rs147327878). Computational prediction tools and conservation a nalysis suggest that the p.Glu262Val variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, wh ile the clinical significance of the p.Glu262Val variant is uncertain, its frequ ency suggests that it is more likely to be benign.
GeneDx	RCV000711441	SCV000235781	uncertain significance	not provided	2023-04-12	criteria provided, single submitter	clinical testing	Variant reported in the published literature in a 24-year-old African American male with reduced ejection fraction, arrhythmia, and family history of cardiomyopathy (Pugh et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24503780, 26807690, 26582918, 29926427)
Eurofins Ntd Llc (ga)	RCV000711441	SCV000344393	uncertain significance	not provided	2018-01-07	criteria provided, single submitter	clinical testing
Invitae	RCV001081604	SCV000654182	likely benign	Desmin-related myofibrillar myopathy	2024-01-31	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000711441	SCV000841807	uncertain significance	not provided	2020-11-11	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002408512	SCV002670935	likely benign	Cardiovascular phenotype	2019-02-27	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.
Revvity Omics, Revvity	RCV000711441	SCV003829012	uncertain significance	not provided	2021-09-13	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003486561	SCV004240482	likely benign	Cardiomyopathy	2023-04-24	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003944906	SCV004765658	likely benign	DES-related disorder	2022-04-06	criteria provided, single submitter	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).
Clinical Genetics, Academic Medical Center	RCV000711441	SCV001917909	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000037252	SCV001965651	benign	not specified		no assertion criteria provided	clinical testing