Submissions for variant NM_004006.3(DMD):c.1554T>A (p.Asp518Glu)

gnomAD frequency: 0.01098  dbSNP: rs61733587

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000080459	SCV000112361	benign	not specified	2013-10-04	criteria provided, single submitter	clinical testing
GeneDx	RCV000080459	SCV000168166	benign	not specified	2014-04-17	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.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000224791	SCV000281446	benign	not provided	2016-01-11	criteria provided, single submitter	clinical testing
Invitae	RCV001084239	SCV000288043	benign	Duchenne muscular dystrophy	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000080459	SCV000309922	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000245475	SCV000319874	benign	Cardiovascular phenotype	2015-07-15	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.
Athena Diagnostics	RCV000224791	SCV001143742	benign	not provided	2019-01-18	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000224791	SCV001157227	benign	not provided	2023-09-21	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001167507	SCV001330014	benign	Dilated cardiomyopathy 3B	2018-01-13	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.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000080459	SCV001433374	likely benign	not specified	2019-04-11	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000080459	SCV001737832	benign	not specified	2021-05-23	criteria provided, single submitter	clinical testing	Variant summary: DMD c.1554T>A (p.Asp518Glu) results in a conservative amino acid change in 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 0.0029 in 183134 control chromosomes in the gnomAD database, including 9 homozygotes. The observed variant frequency is approximately 260 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 benign. To our knowledge, no occurrence of c.1554T>A in individuals affected with Dystrophinopathies and no experimental evidence demonstrating its impact on protein function have been reported. Seven 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.
Fulgent Genetics, Fulgent Genetics	RCV002498414	SCV002811802	likely benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Dilated cardiomyopathy 3B	2022-01-21	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000080459	SCV002034013	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000080459	SCV002035566	benign	not specified		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001826728	SCV002090351	likely benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2017-04-20	no assertion criteria provided	clinical testing