ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.2071G>A (p.Val691Ile)

gnomAD frequency: 0.00284  dbSNP: rs148915045
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 11
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000151220 SCV000199077 likely benign not specified 2015-03-23 criteria provided, single submitter clinical testing p.Val691Ile in exon 18 of MYH6: This variant is not expected to have clinical si gnificance because it has been identified in 0.9% (92/10402) of African chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; d bSNP rs148915045).
GeneDx RCV000151220 SCV000515776 benign not specified 2017-01-06 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 RCV000457574 SCV000557919 benign Hypertrophic cardiomyopathy 14 2023-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000619683 SCV000735996 benign Cardiovascular phenotype 2018-06-11 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000769419 SCV000900812 uncertain significance Cardiomyopathy 2016-04-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000151220 SCV001432120 benign not specified 2020-08-24 criteria provided, single submitter clinical testing Variant summary: MYH6 c.2071G>A (p.Val691Ile) results in a conservative amino acid change located in the Myosin head, motor domain (IPR001609) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00092 in 282834 control chromosomes, predominantly at a frequency of 0.0096 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 384 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 or African-American origin. To our knowledge, no experimental evidence demonstrating its impact on protein function has been reported. One co-occurrence with another pathogenic variant has been internally reported (TTR c.424G>A, p.V142I), providing supporting evidence for a benign role. Five ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (1x), likely benign (1x) and benign (3x). Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001701688 SCV004562151 likely benign not provided 2023-08-16 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004544355 SCV004799754 benign MYH6-related disorder 2019-05-03 criteria provided, single submitter clinical testing This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Clinical Genetics, Academic Medical Center RCV000151220 SCV001925333 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001701688 SCV001931554 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000151220 SCV001974596 benign not specified no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.