Submissions for variant NM_002471.4(MYH6):c.643-5C>T

gnomAD frequency: 0.00041  dbSNP: rs199859986

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037538	SCV000061196	uncertain significance	not specified	2013-03-06	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The 643-5C>T varian t in MYH6 has not been reported in the literature nor previously identified by o ur laboratory. This variant has been identified in 0.1% (7/8600) of European Ame rican chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). This variant is located in the 3' splice re gion. Computational tools do not suggest an impact to splicing. However, this in formation is not predictive enough to rule out pathogenicity. Although this data supports that the 643-5C>T variant may be benign, additional studies are needed to fully assess its clinical significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000230504	SCV000287441	likely benign	Hypertrophic cardiomyopathy 14	2024-12-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000251059	SCV000318281	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.
GeneDx	RCV001528652	SCV000534461	likely benign	not provided	2021-02-04	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26656175)
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769432	SCV000900825	likely benign	Cardiomyopathy	2021-01-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001528652	SCV001747701	likely benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	MYH6: BP4
Blueprint Genetics	RCV000157345	SCV000207082	likely benign	Primary familial hypertrophic cardiomyopathy	2014-11-28	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528652	SCV001740754	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000037538	SCV001919051	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001528652	SCV001932749	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001528652	SCV001957629	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001528652	SCV001968893	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004541110	SCV004788490	likely benign	MYH6-related disorder	2019-09-19	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).