Submissions for variant NM_001018005.2(TPM1):c.23T>A (p.Met8Lys)

dbSNP: rs397516364

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001302170	SCV001491364	uncertain significance	Hypertrophic cardiomyopathy	2024-07-21	criteria provided, single submitter	clinical testing	This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 8 of the TPM1 protein (p.Met8Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TPM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1005318). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Met8Arg amino acid residue in TPM1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22464770, 33020181). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.