Submissions for variant NM_000117.3(EMD):c.445G>C (p.Asp149His)

gnomAD frequency: 0.00019  dbSNP: rs2070818

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000230785	SCV000283517	benign	X-linked Emery-Dreifuss muscular dystrophy	2025-01-30	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000594536	SCV000708250	benign	not specified	2017-05-05	criteria provided, single submitter	clinical testing
GeneDx	RCV000594536	SCV000731039	benign	not specified	2017-11-22	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 Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000853050	SCV000995808	benign	Cardiomyopathy	2017-04-04	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000594536	SCV002547831	benign	not specified	2022-05-25	criteria provided, single submitter	clinical testing	Variant summary: EMD c.445G>C (p.Asp149His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00044 in 205102 control chromosomes (gnomAD), predominantly at a frequency of 0.0058 within the East Asian subpopulation in the gnomAD database, including 31 hemizygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 6 fold of the estimated maximal expected allele frequency for a pathogenic variant in EMD causing Emery-Dreifuss Muscular Dystrophy phenotype (0.001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. Six ClinVar submitters have assessed the variant since 2014: one classified the variant as likely benign and five as benign. Based on the evidence outlined above, the variant was classified as benign.
Ambry Genetics	RCV002327100	SCV002635997	likely benign	Cardiovascular phenotype	2021-01-08	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.
Breakthrough Genomics, Breakthrough Genomics	RCV001310759	SCV005208040	likely benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV001271615	SCV001452891	benign	Emery-Dreifuss muscular dystrophy	2020-09-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000594536	SCV001924085	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001310759	SCV001957850	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001310759	SCV001965491	likely benign	not provided		no assertion criteria provided	clinical testing