ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.1132G>A (p.Gly378Ser) (rs148962966)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000154766 SCV000204446 likely benign not specified 2013-12-26 criteria provided, single submitter clinical testing Gly378Ser in exon 12 of MYH6: This variant is not expected to have clinical sign ificance because it has been identified in 1.0% (6/572) of Asian chromosomes by the 1000 Genomes Project (dbSNP rs148962966). Gly378Ser in exon 12 of MYH6 (rs1 48962966; allele frequency = 1.0%, 6/572)
Ambry Genetics RCV000241733 SCV000319653 likely benign Cardiovascular phenotype 2017-12-12 criteria provided, single submitter clinical testing Subpopulation frequency in support of benign classification;Other data supporting benign classification
Invitae RCV000464311 SCV000557903 benign Familial hypertrophic cardiomyopathy 14 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000154766 SCV000718668 likely benign not specified 2017-04-21 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 RCV001170246 SCV001332806 likely benign Cardiomyopathy 2017-12-27 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000154766 SCV001432004 benign not specified 2020-08-17 criteria provided, single submitter clinical testing Variant summary: MYH6 c.1132G>A (p.Gly378Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00088 in 251172 control chromosomes, including 1 homozygote (gnomAD). The variant was found at a frequency of 0.006 within the East Asian subpopulation, this frequency is approximately 230-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. To our knowledge, no occurrence of c.1132G>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (1x) / likely benign (3x). Based on the evidence outlined above, the variant was classified as benign.

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