ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.1763A>C (p.Asp588Ala)

gnomAD frequency: 0.00153  dbSNP: rs142992009
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 19
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000172566 SCV000051407 likely benign not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000151221 SCV000199079 uncertain significance not specified 2013-08-02 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Asp588Ala varia nt in MYH6 is present in 0.2% (19/8600) of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs142992 009). It has also been reported in 1 individual with CHD (Granados-Riveron 2010) . Computational analyses (biochemical amino acid properties, conservation, Align GVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impac t to the protein. The variant?s population frequency suggests that it is more li kely benign but is too low to confidently rule out a disease-causing role. Addit ional information is needed to fully assess its clinical significance.
Eurofins Ntd Llc (ga) RCV000151221 SCV000226269 likely benign not specified 2015-06-05 criteria provided, single submitter clinical testing
Invitae RCV000989183 SCV000287397 likely benign Hypertrophic cardiomyopathy 14 2024-01-29 criteria provided, single submitter clinical testing
GeneDx RCV000172566 SCV000513788 likely benign not provided 2021-04-14 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 22955375, 8282798, 26085007, 20656787, 23396983, 28074886, 27789736, 23861362, 27760138, 27607113, 26284702, 21378987, 22194935, 19864899, 19808347, 15998695, 14573521, 8878443, 2969919)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000151221 SCV000697923 likely benign not specified 2020-11-24 criteria provided, single submitter clinical testing Variant summary: MYH6 c.1763A>C (p.Asp588Ala) results in a non-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 0.0018 in 252206 control chromosomes, predominantly at a frequency of 0.0032 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 128 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 Non-Finnish European origin. c.1763A>C has been reported in the literature in individuals affected with Cardiomyopathy (Theis_2015, Lopes_2015, Christiansen_2016, Neubauer_2017, Mates_2018, Jaaskelainen_2019). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight ClinVar submitters (evaluation after 2014) cite the variant as benign (1x), likely benign (6x) and uncertain significance (1x). Based on the evidence outlined above, the variant was classified as likely benign.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000151221 SCV000740615 likely benign not specified 2016-09-08 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000172566 SCV000884187 likely benign not provided 2020-08-17 criteria provided, single submitter clinical testing
Mendelics RCV000989183 SCV001139405 benign Hypertrophic cardiomyopathy 14 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000172566 SCV001149146 benign not provided 2024-02-01 criteria provided, single submitter clinical testing MYH6: BS1, BS2
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001798462 SCV002043176 benign Cardiomyopathy 2019-05-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV002408642 SCV002716770 likely benign Cardiovascular phenotype 2019-03-25 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.
PreventionGenetics, part of Exact Sciences RCV004532623 SCV004720370 likely benign MYH6-related disorder 2020-10-26 criteria provided, single submitter 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).
Blueprint Genetics RCV000143919 SCV000188793 benign Primary familial hypertrophic cardiomyopathy 2014-12-05 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000172566 SCV001744409 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000151221 SCV001920957 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000172566 SCV001930035 likely benign not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000151221 SCV001953424 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000172566 SCV001971278 likely benign not provided 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.