ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.1131C>T (p.Asp377=) (rs61742472)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000219999 SCV000270445 likely benign not specified 2015-05-06 criteria provided, single submitter clinical testing p.Asp377Asp in exon 12 of MYH6: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 0.2% (18/10384) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP rs61742472).
Ambry Genetics RCV000247644 SCV000319800 likely benign Cardiovascular phenotype 2015-06-29 criteria provided, single submitter clinical testing
GeneDx RCV000219999 SCV000532856 likely benign not specified 2018-01-16 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 RCV000769424 SCV000900817 likely benign Cardiomyopathy 2016-10-12 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000845502 SCV000987604 likely benign not provided criteria provided, single submitter clinical testing
Invitae RCV001088244 SCV001002097 benign Familial hypertrophic cardiomyopathy 14 2019-12-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000219999 SCV001360439 benign not specified 2019-03-25 criteria provided, single submitter clinical testing Variant summary: MYH6 c.1131C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00023 in 276770 control chromosomes, predominantly at a frequency of 0.0017 within the African subpopulation in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately 68 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. To our knowledge, no occurrence of c.1131C>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (X3 likely benign and X3 uncertain significance). Based on the evidence outlined above, the variant was classified as benign.

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