Submissions for variant NM_004006.3(DMD):c.1869C>T (p.Leu623=)

dbSNP: rs1800267

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000080468	SCV000112370	benign	not specified	2014-04-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000080468	SCV000168168	benign	not specified	2014-03-28	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	RCV000080468	SCV000268947	benign	not specified	2015-01-13	criteria provided, single submitter	clinical testing	p.Leu623Leu in exon 16 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 10.9% (418/3833) of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs. gs.washington.edu/EVS/; dbSNP rs1800267).
PreventionGenetics, part of Exact Sciences	RCV000080468	SCV000309924	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000245650	SCV000318586	benign	Cardiovascular phenotype	2015-10-20	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	RCV000285906	SCV000482273	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.
Invitae	RCV000470353	SCV000560810	benign	Duchenne muscular dystrophy	2024-01-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000711449	SCV000603341	benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000711449	SCV000841816	benign	not provided	2017-10-09	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000080468	SCV000919264	benign	not specified	2018-07-13	criteria provided, single submitter	clinical testing	Variant summary: DMD c.1869C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.011 in 200065 control chromosomes, predominantly at a frequency of 0.11 within the African subpopulation in the gnomAD database, including 93 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 9.84 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 origin. To our knowledge, no occurrence of c.1869C>T in individuals affected with Dystrophiopathies and no experimental evidence demonstrating its impact on protein function have been reported. Five 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.
Natera, Inc.	RCV001826730	SCV002092222	benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2017-04-21	no assertion criteria provided	clinical testing