Submissions for variant NM_000257.4(MYH7):c.345C>T (p.Tyr115=)

gnomAD frequency: 0.00011  dbSNP: rs149439730

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035855	SCV000059506	likely benign	not specified	2018-09-05	criteria provided, single submitter	clinical testing	proposed classification - variant undergoing re-assessment, contact laboratory
Labcorp Genetics (formerly Invitae), Labcorp	RCV000466410	SCV000546176	uncertain significance	Hypertrophic cardiomyopathy	2025-02-02	criteria provided, single submitter	clinical testing	This sequence change affects codon 115 of the MYH7 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MYH7 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs149439730, gnomAD 0.05%). This variant has been observed in individual(s) with dilated cardiomyopathy (internal data). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 42962). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Diagnostics, LLC DBA Color Health	RCV001190179	SCV001357614	likely benign	Cardiomyopathy	2019-12-16	criteria provided, single submitter	clinical testing
GeneDx	RCV001650859	SCV001869771	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001190179	SCV002042666	likely benign	Cardiomyopathy	2019-08-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002453301	SCV002613016	likely benign	Cardiovascular phenotype	2019-09-24	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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001650859	SCV002035043	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001650859	SCV002037505	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001650859	SCV002037759	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004534743	SCV004742506	likely benign	MYH7-related disorder	2023-08-18	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).