ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.1305G>A (p.Met435Ile)

gnomAD frequency: 0.00001  dbSNP: rs863224644
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000197853 SCV000254441 uncertain significance Hypertrophic cardiomyopathy 2022-01-16 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 435 of the MYH7 protein (p.Met435Ile). 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. This variant is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 216362). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This variant is not present in population databases (gnomAD no frequency).
Ambry Genetics RCV002381688 SCV002693531 uncertain significance Cardiovascular phenotype 2023-05-16 criteria provided, single submitter clinical testing The p.M435I variant (also known as c.1305G>A), located in coding exon 12 of the MYH7 gene, results from a G to A substitution at nucleotide position 1305. The methionine at codon 435 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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