ClinVar Miner

Submissions for variant NM_002471.3(MYH6):c.5137G>A (p.Glu1713Lys) (rs369275573)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000250543 SCV000318049 uncertain significance Cardiovascular phenotype 2013-01-29 criteria provided, single submitter clinical testing
Invitae RCV000465457 SCV000546156 uncertain significance Familial hypertrophic cardiomyopathy 14 2016-07-29 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1713 of the MYH6 protein (p.Glu1713Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs369275573, ExAC 0.01%) but has not been reported in the literature in individuals with a MYH6-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000520603 SCV000618856 uncertain significance not provided 2017-07-10 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MYH6 gene. The E1713K variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The E1713K 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 and in silico analysis predicts this variant is probably damaging to the protein structure/function.

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