Submissions for variant NM_004006.3(DMD):c.1934A>G (p.Asp645Gly)

gnomAD frequency: 0.00036  dbSNP: rs147822019

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000305211	SCV000332219	likely benign	not specified	2016-08-29	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000514379	SCV000609970	likely benign	not provided	2017-03-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000514379	SCV000729528	benign	not provided	2020-12-21	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 7981690, 24274981, 25220406)
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000305211	SCV000740565	likely benign	not specified	2017-01-27	criteria provided, single submitter	clinical testing
Invitae	RCV001082933	SCV001002170	benign	Duchenne muscular dystrophy	2024-01-27	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000514379	SCV001155973	uncertain significance	not provided	2019-05-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000305211	SCV001362908	likely benign	not specified	2022-02-18	criteria provided, single submitter	clinical testing	Variant summary: DMD c.1934A>G (p.Asp645Gly) results in a non-conservative amino acid change located in the Rod domain (Prior_1994) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00027 in 183396 control chromosomes. The observed variant frequency is approximately 24.72 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. c.1934A>G has been reported in the literature in individuals affected with DMD (Prior_1994). This report does not provide unequivocal conclusions about association of the variant with Dystrophinopathies. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Six submitters classified as likely benign/benign while one classified as VUS. Based on the evidence outlined above, the variant was classified as likely benign.
Ambry Genetics	RCV002411145	SCV002721318	benign	Cardiovascular phenotype	2022-08-24	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.
PreventionGenetics, part of Exact Sciences	RCV004542986	SCV004785676	likely benign	DMD-related disorder	2021-03-09	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).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000514379	SCV001740474	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000305211	SCV001975543	benign	not specified		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001833309	SCV002092213	likely benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2020-01-22	no assertion criteria provided	clinical testing