Submissions for variant NM_000117.3(EMD):c.396C>T (p.His132=)

gnomAD frequency: 0.00077  dbSNP: rs145985318

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035106	SCV000058746	likely benign	not specified	2009-05-05	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000035106	SCV000342536	benign	not specified	2016-10-05	criteria provided, single submitter	clinical testing
GeneDx	RCV000035106	SCV000512930	benign	not specified	2015-07-02	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.
Invitae	RCV000474105	SCV000560793	benign	X-linked Emery-Dreifuss muscular dystrophy	2024-02-01	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000035106	SCV000613253	benign	not specified	2017-04-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000621249	SCV000736790	benign	Cardiovascular phenotype	2017-03-07	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770589	SCV000902038	likely benign	Cardiomyopathy	2017-04-13	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000035106	SCV001363451	benign	not specified	2019-01-21	criteria provided, single submitter	clinical testing	Variant summary: EMD c.396C>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 0.00081 in 199766 control chromosomes, including 61 hemizygotes (gnomAD). c.396C>T has been reported in the literature in one individual affected with Dilated Cardiomyopathy and was classified by the authors as likely benign (Pugh_2014). This report does not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Fulgent Genetics, Fulgent Genetics	RCV000474105	SCV002806030	benign	X-linked Emery-Dreifuss muscular dystrophy	2021-09-23	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003934887	SCV004753580	likely benign	EMD-related condition	2024-02-01	criteria provided, single submitter	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).
Clinical Genetics, Academic Medical Center	RCV000035106	SCV001922007	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001727518	SCV001969046	likely benign	not provided		no assertion criteria provided	clinical testing