Submissions for variant NM_002471.4(MYH6):c.4960-17A>T

gnomAD frequency: 0.03950  dbSNP: rs28730764

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000245828	SCV000052977	benign	not specified	2019-10-29	criteria provided, single submitter	clinical testing	Variant summary: MYH6 c.4960-17A>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 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 0.014 in 250952 control chromosomes in the gnomAD database, including 142 homozygotes. The observed variant frequency is approximately 546 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYH6 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.4960-17A>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter (evaluation after 2014) cites the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
PreventionGenetics, part of Exact Sciences	RCV000245828	SCV000308986	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000245828	SCV000513791	benign	not specified	2016-10-13	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002054510	SCV002428484	benign	Hypertrophic cardiomyopathy 14	2025-02-04	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV004706449	SCV005232842	benign	not provided		criteria provided, single submitter	not provided
Clinical Genetics, Academic Medical Center	RCV000245828	SCV001919969	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000245828	SCV001956862	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000245828	SCV001964493	benign	not specified		no assertion criteria provided	clinical testing