Submissions for variant NM_002471.4(MYH6):c.4595G>T (p.Arg1532Leu)

dbSNP: rs34330111

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154756	SCV000204436	uncertain significance	not specified	2013-09-09	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The Arg1532Leu vari ant in MYH6 has not been reported in individuals with cardiomyopathy, but has be en identified in 0.2% (9/4406) of African American chromosomes by the NHLBI Exom e Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs34330111). Comp utational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to t he protein. While the frequency of this variant suggests that it is more likely benign, it is too low to confidently rule out a disease-causing role. Additional information is needed to fully assess the clinical significance of this variant .
Labcorp Genetics (formerly Invitae), Labcorp	RCV000228396	SCV000287429	likely benign	Hypertrophic cardiomyopathy 14	2024-10-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001719961	SCV000616985	likely benign	not provided	2020-05-20	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000620512	SCV000736263	likely benign	Cardiovascular phenotype	2018-04-09	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.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000623367	SCV000740622	uncertain significance	Primary familial hypertrophic cardiomyopathy	2017-03-21	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852692	SCV000995402	likely benign	Cardiomyopathy	2018-04-23	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004544411	SCV004784641	likely benign	MYH6-related disorder	2020-04-13	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).
Zaffran Lab, Genetics of Cardiac Diseases Laboratory, Marseille Medical Genetics	RCV004765315	SCV005374736	uncertain significance	Hypertrophic cardiomyopathy		no assertion criteria provided	research