ClinVar Miner

Submissions for variant NM_002471.3(MYH6):c.3469G>A (p.Gly1157Arg) (rs755974106)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000424194 SCV000535201 uncertain significance not provided 2016-12-20 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MYH6 gene. The G1157R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project (average read depth 9.0). The G1157R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. Finally, in silico analysis predicts this variant is probably damaging to the protein structure/function.
Invitae RCV000802894 SCV000942743 uncertain significance Familial hypertrophic cardiomyopathy 14 2018-11-16 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 1157 of the MYH6 protein (p.Gly1157Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with MYH6-related disease. ClinVar contains an entry for this variant (Variation ID: 392010). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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