Submissions for variant NM_002471.4(MYH6):c.2579G>A (p.Arg860His)

gnomAD frequency: 0.00573  dbSNP: rs115845031

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000037458	SCV000054815	benign	not specified	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037458	SCV000061116	benign	not specified	2012-05-10	criteria provided, single submitter	clinical testing	Arg860His in Exon 21 of MYH6: This variant is not expected to have clinical sign ificance because it has been identified in 1.7% (64/3738) of African American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS; dbSNP rs115845031).
Invitae	RCV001082478	SCV000287399	benign	Hypertrophic cardiomyopathy 14	2024-01-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000242007	SCV000318382	benign	Cardiovascular phenotype	2016-03-29	criteria provided, single submitter	clinical testing	This alteration is classified as 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	RCV000037458	SCV000515733	benign	not specified	2016-11-18	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770454	SCV000901897	likely benign	Cardiomyopathy	2016-02-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000037458	SCV000919828	benign	not specified	2018-08-06	criteria provided, single submitter	clinical testing	Variant summary: MYH6 c.2579G>A (p.Arg860His) results in a non-conservative amino acid change located in the Myosin tail of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0017 in 277230 control chromosomes, predominantly at a frequency of 0.017 within the African subpopulation in the gnomAD database, including 3 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 679.99 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 a benign polymorphism found primarily in populations of African origin. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000845565	SCV000987695	uncertain significance	not provided		criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000770454	SCV000995408	benign	Cardiomyopathy	2019-06-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000845565	SCV003799664	likely benign	not provided	2023-10-16	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000845565	SCV001744001	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000037458	SCV001920968	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000037458	SCV001969405	benign	not specified		no assertion criteria provided	clinical testing