Submissions for variant NM_004006.3(DMD):c.4093C>T (p.Leu1365Phe)

gnomAD frequency: 0.00071  dbSNP: rs148781346

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000235165	SCV000112502	likely benign	not specified	2016-01-13	criteria provided, single submitter	clinical testing
GeneDx	RCV001703996	SCV000235869	benign	not provided	2021-05-17	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000476221	SCV000560842	likely benign	Duchenne muscular dystrophy	2024-01-16	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000235165	SCV000711684	uncertain significance	not specified	2017-05-22	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Leu1365Phe va riant in DMD has not been previously reported in individuals with muscular dystr ophy, but has been identified in 0.19% (35/18082) of African chromosomes by the genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; dbSNP rs 148781346). This variant has been reported in ClinVar (Variation ID: 94611). Ple ase note that for diseases with clinical variability, reduced penetrance, or rec essive inheritance, pathogenic variants may be present at a low frequency in the general population. Computational prediction tools and conservation analysis su ggest that the p.Leu1365Phe variant may impact the protein, though this informat ion is not predictive enough to determine pathogenicity. In summary, while the c linical significance of the p.Leu1365Phe variant is uncertain, its frequency sug gests that it is more likely to be benign.
Ambry Genetics	RCV002321578	SCV002628995	likely benign	Cardiovascular phenotype	2019-03-26	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000235165	SCV003922913	likely benign	not specified	2023-03-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004542776	SCV004771399	likely benign	DMD-related disorder	2020-10-30	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).