ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.3010G>T (p.Ala1004Ser)

gnomAD frequency: 0.00110  dbSNP: rs143978652
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Total submissions: 22
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000172563 SCV000051405 likely benign Primary dilated cardiomyopathy 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000037468 SCV000061126 likely benign not specified 2015-07-16 criteria provided, single submitter clinical testing p.Ala1004Ser in exon 23 of MYH6: This variant is not expected to have clinical s ignificance because it has been identified in 0.3% (31/11578) of Latino chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; d bSNP rs143978652).
Scripps Translational Science Institute, Scripps Health and The Scripps Research Institute RCV000190123 SCV000243765 likely pathogenic Hypertrophic cardiomyopathy 14; Sudden cardiac death 2015-05-29 criteria provided, single submitter research
Laboratory of Genetics and Molecular Cardiology, University of São Paulo RCV000201499 SCV000256193 uncertain significance Hypertrophic cardiomyopathy 14 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000037468 SCV000308969 likely benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000244450 SCV000319519 likely benign Cardiovascular phenotype 2019-03-01 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 RCV000037468 SCV000513789 likely benign not specified 2017-09-08 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.
Invitae RCV000201499 SCV000557899 likely benign Hypertrophic cardiomyopathy 14 2024-01-24 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000623034 SCV000740607 uncertain significance Primary familial hypertrophic cardiomyopathy 2016-06-30 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000723680 SCV000884189 likely benign not provided 2020-05-15 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000770446 SCV000901889 likely benign Cardiomyopathy 2019-03-22 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego RCV000852696 SCV000995407 likely benign Primary dilated cardiomyopathy; Ventricular tachycardia 2019-03-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000037468 SCV001360441 likely benign not specified 2019-07-29 criteria provided, single submitter clinical testing Variant summary: MYH6 c.3010G>T (p.Ala1004Ser) results in a conservative amino acid change located in the Myosin tail domain (IPR002928) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00093 in 251486 control chromosomes, predominantly at a frequency of 0.0021 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 84 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 Latino origin. c.3010G>T has been reported in the literature in sequencing studies among individuals affected with Cardiomyopathy (Carniel_2005, Brion_2009, Brion_2012, Hershberger_2010, Posch_2011, Waldmuller_2010-unpublished poster, Merlo_2013). These data indicate that the variant may be associated with disease. At-least one co-occurrence with other pathogenic variant(s) has been reported (MYH7 c.1988G>A, p.R663H), providing supporting evidence for a benign role (Waldmuller_2010, unpublished poster abstract). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments. Based on the evidence outlined above, the variant was classified as likely benign.
CeGaT Center for Human Genetics Tuebingen RCV000723680 SCV003917313 benign not provided 2023-05-01 criteria provided, single submitter clinical testing MYH6: BS1, BS2
OMIM RCV000015214 SCV000035471 pathogenic Dilated cardiomyopathy 1EE 2005-07-05 flagged submission literature only
Eurofins Ntd Llc (ga) RCV000723680 SCV000082834 uncertain significance not provided 2013-06-11 flagged submission clinical testing
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000656144 SCV000678338 likely pathogenic Wolff-Parkinson-White pattern 2017-07-14 flagged submission research This variant was identified in an individual with Wolff-Parkinson-White syndrome
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000723680 SCV001740026 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000723680 SCV001921063 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000723680 SCV001930957 likely benign not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000723680 SCV001959991 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000723680 SCV001969127 likely benign not provided no assertion criteria provided clinical testing

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