ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.2946G>A (p.Glu982=) (rs145274612)

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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 RCV000037466 SCV000061124 benign not specified 2012-01-27 criteria provided, single submitter clinical testing Glu982Glu in exon 23 of MYH6: This variant is classified as benign based on its high frequency in the general population (dbSNP rs145274612; NHLBI Exome Sequenc ing Project,
Invitae RCV000234739 SCV000287402 benign Familial hypertrophic cardiomyopathy 14 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000244702 SCV000317890 benign Cardiovascular phenotype 2014-12-18 criteria provided, single submitter clinical testing
GeneDx RCV000037466 SCV000515357 benign not specified 2016-11-08 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 RCV000770447 SCV000901890 benign Cardiomyopathy 2015-11-18 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000037466 SCV000917839 benign not specified 2018-05-29 criteria provided, single submitter clinical testing Variant summary: MYH6 c.2946G>A 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 0.011 in 277200 control chromosomes in the gnomAD database, including 37 homozygotes. The observed variant frequency is approximately 439-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in MYH6 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. The variant, c.2946G>A, has been reported in the literature in individuals affected with Cardiomyopathy (Posch_2011). This report does not provide an unequivocal conclusion about the association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "likely benign/benign." Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000037466 SCV001157077 benign not specified 2019-05-05 criteria provided, single submitter clinical testing

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