Submissions for variant NM_004006.3(DMD):c.1731A>T (p.Glu577Asp)

gnomAD frequency: 0.00073  dbSNP: rs150199251

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723549	SCV000112366	uncertain significance	not provided	2018-09-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000235164	SCV000235863	likely benign	not specified	2017-04-14	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.
Ambry Genetics	RCV000619753	SCV000736194	likely benign	Cardiovascular phenotype	2018-07-25	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079116	SCV000751561	benign	Duchenne muscular dystrophy	2024-01-25	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000723549	SCV000987526	likely benign	not provided		criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000235164	SCV001339230	benign	not specified	2020-03-30	criteria provided, single submitter	clinical testing	Variant summary: DMD c.1731A>T (p.Glu577Asp) 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 0.00019 in 183229 control chromosomes (including 17/75917 hemizygotes). The observed variant frequency is approximately 17 fold of the estimated maximal expected allele frequency for a pathogenic variant in DMD causing Dystrophinopathies phenotype (1.1e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1731A>T in individuals affected with Dystrophinopathies and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (likely benign/benign n=3, VUS n=1). Based on the evidence outlined above, the variant was classified as benign.
Natera, Inc.	RCV001831832	SCV002092244	likely benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2018-04-27	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004542773	SCV004757027	likely benign	DMD-related disorder	2023-06-08	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).