ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.4294G>A (p.Val1432Ile) (rs144200285)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000712357 SCV000842831 uncertain significance not provided 2018-06-06 criteria provided, single submitter clinical testing
GeneDx RCV000712357 SCV000621970 uncertain significance not provided 2017-11-02 criteria provided, single submitter clinical testing The V1432I variant of uncertain significance in the MYH7 gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 4/24,034 alleles from individuals of African ancestry and 3/126,664 alleles from individuals of European (non-Finnish) ancestry in large population cohorts (Lek et al., 2016). The V1432I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to valine are tolerated across species. Furthermore, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Invitae RCV000798106 SCV000937705 uncertain significance Hypertrophic cardiomyopathy 2018-09-26 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 1432 of the MYH7 protein (p.Val1432Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs144200285, ExAC 0.02%). This variant has not been reported in the literature in individuals with MYH7-related disease. ClinVar contains an entry for this variant (Variation ID: 453109). 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: "Not Available"; 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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