Submissions for variant NM_004006.3(DMD):c.2827C>T (p.Arg943Cys)

gnomAD frequency: 0.00021  dbSNP: rs199986217

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000080527	SCV000112429	benign	not specified	2016-05-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000845504	SCV000520969	benign	not provided	2019-07-09	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25474345, 25231023)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000990698	SCV000625881	benign	Duchenne muscular dystrophy	2025-01-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000618497	SCV000736119	benign	Cardiovascular phenotype	2017-12-27	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.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000845504	SCV000987606	likely benign	not provided		criteria provided, single submitter	clinical testing
Mendelics	RCV000990698	SCV001141724	likely benign	Duchenne muscular dystrophy	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001167433	SCV001329933	uncertain significance	Dilated cardiomyopathy 3B	2017-05-01	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000080527	SCV001364026	benign	not specified	2019-02-15	criteria provided, single submitter	clinical testing	Variant summary: DMD c.2827C>T (p.Arg943Cys) results in a non-conservative amino acid change located in the Spectrin/alpha-actinin repeat of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00018 in 199644 control chromosomes, including 14 hemizygotes (gnomAD). The high occurrence in hemizygous control individuals suggests this variant is benign. DMD gene is found to be tolerant to missense changes (Z = -4.82, ExAC) providing further evidence in support of a benign role for the variant. c.2827C>T has been reported in the literature in individuals affected with Stargardt macular dystrophy and dilated cardiomyopathy (Haas_2015, Zaneveld_2015). These reports do not provide unequivocal conclusions about association of the variant with Dystrophiopathies. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as benign (3x) and once as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Natera, Inc.	RCV001831839	SCV002089667	likely benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2017-11-15	no assertion criteria provided	clinical testing