ClinVar Miner

Submissions for variant NM_002471.3(MYH6):c.1521T>G (p.Ile507Met) (rs142410102)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000765152 SCV000896381 uncertain significance Familial hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Familial hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000498773 SCV000590644 uncertain significance not provided 2017-06-16 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MYH6 gene. The I507M variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). 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. However, the I507M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties.
Invitae RCV000559203 SCV000648225 uncertain significance Familial hypertrophic cardiomyopathy 14 2017-02-17 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with methionine at codon 507 of the MYH6 protein (p.Ile507Met). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and methionine. The frequency data for this variant (rs142410102) in the population databases is unreliable, as metrics indicate poor quality at this position in the ExAC database. This variant 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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