Submissions for variant NM_004006.3(DMD):c.5182C>T (p.Arg1728Cys)

gnomAD frequency: 0.00327  dbSNP: rs34102501

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000212487	SCV000112548	likely benign	not specified	2015-09-17	criteria provided, single submitter	clinical testing
GeneDx	RCV000212487	SCV000235841	benign	not specified	2015-04-21	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.
Invitae	RCV001085478	SCV000560808	benign	Duchenne muscular dystrophy	2024-01-31	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000514541	SCV000609624	likely benign	not provided	2017-08-28	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000212487	SCV000711683	benign	not specified	2017-08-10	criteria provided, single submitter	clinical testing	p.Arg1728Cys in exon 37 of DMD: This variant is classified as benign because it has been identified in 0.9% (180/18042) of African chromosomes, including 48 hem izygotes and 1 homozygote, by the Genome Aggregation Database (gnomAD, http://gn omad.broadinstitute.org; dbSNP rs34102501).
Ambry Genetics	RCV000621386	SCV000735588	benign	Cardiovascular phenotype	2016-11-03	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000514541	SCV000885287	benign	not provided	2017-11-01	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000514541	SCV001143750	benign	not provided	2019-01-09	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001167365	SCV001329855	uncertain significance	Dilated cardiomyopathy 3B	2017-04-28	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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled 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	RCV000212487	SCV001360772	benign	not specified	2019-12-13	criteria provided, single submitter	clinical testing	Variant summary: DMD c.5182C>T (p.Arg1728Cys) results in a non-conservative amino acid change located in the central rod domain 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 0.00099 in 203656 control chromosomes, predominantly at a frequency of 0.0097 within the African or African-American subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 880 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 a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Seven ClinVar submitters (evaluation after 2014) cite the variant as benign (5x) and likely benign (2x). Based on the evidence outlined above, the variant was classified as benign.
PreventionGenetics, part of Exact Sciences	RCV004537360	SCV004750797	benign	DMD-related disorder	2019-06-10	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000514541	SCV001797546	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000212487	SCV001972003	benign	not specified		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000514541	SCV001978557	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001826752	SCV002093529	likely benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2017-08-09	no assertion criteria provided	clinical testing