Submissions for variant NM_004006.3(DMD):c.1318G>A (p.Glu440Lys)

gnomAD frequency: 0.00010  dbSNP: rs189143447

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000183380	SCV000235825	likely benign	not provided	2014-05-20	criteria provided, single submitter	clinical testing	The variant is found in CARDIOMYOPATHY panel(s).
Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center	RCV000148465	SCV000267290	uncertain significance	Becker muscular dystrophy	2016-03-18	criteria provided, single submitter	reference population
PreventionGenetics, part of Exact Sciences	RCV000254538	SCV000309921	likely benign	not specified		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000990731	SCV000625837	benign	Duchenne muscular dystrophy	2024-01-22	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000254538	SCV000702358	benign	not specified	2016-11-21	criteria provided, single submitter	clinical testing
Mendelics	RCV000990731	SCV001141761	benign	Duchenne muscular dystrophy	2019-05-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000254538	SCV001364027	benign	not specified	2019-02-28	criteria provided, single submitter	clinical testing	Variant summary: DMD c.1318G>A (p.Glu440Lys) results in a conservative amino acid change located in the Spectrin/alpha-actinin repeat 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 0.00043 in 195664 control chromosomes, predominantly at a frequency of 0.0053 within the East Asian subpopulation in the gnomAD database, including 24 hemizygotes. This frequency is significantly higher than expected for a pathogenic variant in DMD causing Dystrophinopathies, strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.1318G>A has been reported in the literature in a family affected with Becker muscular dystrophy and it was found in cis with a pathogenic variant (DMD deletion of exons 45 to 53) in 3 affected males and 2 female carriers (Li_2012), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as benign and a submission derived from reference population cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV000183380	SCV001500610	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	DMD: BS2
Ambry Genetics	RCV002381455	SCV002691735	likely benign	Cardiovascular phenotype	2019-07-24	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
CSER _CC_NCGL, University of Washington	RCV000148465	SCV000190165	uncertain significance	Becker muscular dystrophy	2014-06-01	no assertion criteria provided	research
Natera, Inc.	RCV001276610	SCV001463039	uncertain significance	Dystrophin deficiency	2020-04-23	no assertion criteria provided	clinical testing