Submissions for variant NM_004006.3(DMD):c.3406A>T (p.Thr1136Ser)

gnomAD frequency: 0.00356  dbSNP: rs3827462

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000080576	SCV000112478	benign	not specified	2013-07-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000080576	SCV000168175	benign	not specified	2014-04-07	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.
CSER _CC_NCGL, University of Washington	RCV000211434	SCV000212214	likely benign	Primary dilated cardiomyopathy	2015-03-11	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000080576	SCV000268955	benign	not specified	2015-06-04	criteria provided, single submitter	clinical testing	p.Thr1136Ser in exon 25 of DMD: This variant is not expected to have clinical si gnificance because it has been identified in 7% (451/6490) of South Asian chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs3827462).
Ambry Genetics	RCV000249350	SCV000318913	benign	Cardiovascular phenotype	2016-06-24	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	RCV000313769	SCV000482265	likely benign	Dilated cardiomyopathy 3B	2017-04-27	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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae	RCV000470917	SCV000560870	benign	Duchenne muscular dystrophy	2024-02-01	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000991899	SCV001143747	benign	not provided	2019-04-10	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000080576	SCV001572411	benign	not specified	2021-04-07	criteria provided, single submitter	clinical testing	Variant summary: DMD c.3406A>T (p.Thr1136Ser) results in a conservative amino acid change located in the Central rod domain (Repeat 7) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.012 in 175573 control chromosomes, predominantly at a frequency of 0.05 within the South Asian subpopulation in the gnomAD database, including 18 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 4533 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 South Asian origin. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submitters (evaluation after 2014) cite the variant as benign (n=4) and likely benign (n=2). Based on the evidence outlined above, the variant was classified as benign.
Natera, Inc.	RCV001826745	SCV002085449	benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2017-04-21	no assertion criteria provided	clinical testing