ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.1763A>C (p.Asp588Ala) (rs142992009)

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Total submissions: 16
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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 RCV000172566 SCV000051407 likely benign not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Partners HealthCare 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000151221 SCV000226269 likely benign not specified 2015-06-05 criteria provided, single submitter clinical testing
Invitae RCV000989183 SCV000287397 likely benign Familial hypertrophic cardiomyopathy 14 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000249428 SCV000318269 uncertain significance Inborn genetic diseases 2020-01-28 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 RCV001282634 SCV000884187 likely benign none provided 2020-08-17 criteria provided, single submitter clinical testing
Mendelics RCV000989183 SCV001139405 benign Familial hypertrophic cardiomyopathy 14 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000172566 SCV001149146 likely benign not provided 2017-05-01 criteria provided, single submitter clinical testing
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
Human Genetics - Radboudumc,Radboudumc RCV000151221 SCV001953424 benign not specified no assertion criteria provided clinical testing

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