ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.1544T>C (p.Met515Thr)

dbSNP: rs863224900
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UCLA Clinical Genomics Center, UCLA RCV003320136 SCV000255419 likely pathogenic Hypertrophic cardiomyopathy 1; Myosin storage myopathy; Dilated cardiomyopathy 1S; MYH7-related skeletal myopathy 2012-12-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003586165 SCV004296285 likely pathogenic Hypertrophic cardiomyopathy 2024-01-13 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 515 of the MYH7 protein (p.Met515Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of MYH7-related conditions (PMID: 18953637, 25326637, 27532257). ClinVar contains an entry for this variant (Variation ID: 216968). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH7 protein function with a positive predictive value of 95%. This variant disrupts the p.Met515 amino acid residue in MYH7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15358028; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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