Submissions for variant NM_004006.3(DMD):c.837G>A (p.Thr279=)

gnomAD frequency: 0.12849  dbSNP: rs1800265

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000080798	SCV000112700	benign	not specified	2015-11-11	criteria provided, single submitter	clinical testing
GeneDx	RCV000080798	SCV000168164	benign	not specified	2014-01-17	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000080798	SCV000268973	benign	not specified	2015-01-13	criteria provided, single submitter	clinical testing	p.Thr279Thr in exon 09 of DMD: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 48% (1838/3833) of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.g s.washington.edu/EVS/; dbSNP rs1800265).
PreventionGenetics, part of Exact Sciences	RCV000080798	SCV000309946	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000242257	SCV000317821	benign	Cardiovascular phenotype	2015-06-26	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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.
Illumina Laboratory Services, Illumina	RCV000292926	SCV000482279	benign	Dilated cardiomyopathy 3B	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001811377	SCV000603336	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000576553	SCV000677279	benign	Becker muscular dystrophy; Duchenne muscular dystrophy	2017-04-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000080798	SCV000919265	benign	not specified	2018-07-19	criteria provided, single submitter	clinical testing	Variant summary: DMD c.837G>A results in a synonymous change. The variant allele was found at a frequency of 0.087 in 40353 control chromosomes, predominantly at a frequency of 0.52 within the African or African-American subpopulation in the ExAC database, including 620 homozygotes. The observed variant frequency within African or African-American control individuals in the ExAC database is approximately 46.51 fold of the estimated maximal expected allele frequency for a pathogenic variant in DMD causing Dystrophiopathies phenotype (0.011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.837G>A in individuals affected with Dystrophiopathies and no experimental evidence demonstrating its impact on protein function have been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae	RCV001511774	SCV001719071	benign	Duchenne muscular dystrophy	2024-02-01	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001835680	SCV002090459	benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2017-04-20	no assertion criteria provided	clinical testing