Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000824326 | SCV000965220 | uncertain significance | Hypertrophic cardiomyopathy | 2021-12-09 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 665938). This missense change has been observed in individual(s) with clinical features of TPM1-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 238 of the TPM1 protein (p.Arg238Leu). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant disrupts the p.Arg238 amino acid residue in TPM1. Other variant(s) that disrupt this residue have been observed in individuals with TPM1-related conditions (Invitae), which suggests that this may be a clinically significant amino acid residue. 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. |