Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000036368 | SCV000060020 | uncertain significance | not specified | 2013-08-27 | criteria provided, single submitter | clinical testing | The Met281Val variant in TPM1 has now been identified by our laboratory in 2 Cau casian individuals with HCM, though it did not segregate with disease in one aff ected relative. This variant has not been identified in large population studies . Conservation and other computational analyses are unreliable for this exon. Fi nally, another variant of unknown significance has been reported at this positio n in two patients with HCM (Met281Thr; Van Driest 2003, LMM unpublished data). I n summary, additional information is needed to fully assess the clinical signifi cance of this variant. |
Gene |
RCV000766955 | SCV000209335 | uncertain significance | not provided | 2023-09-29 | criteria provided, single submitter | clinical testing | Identified in a patient with HCM who also harbored a second variant in the TPM1 gene (Lamounier et al., 2021); this variant was also identified in this individual's brother who died suddenly at age 40; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28797094, 23886664, 25342278, 27532257, 34699384, 31983221, 33642254, 28771489) |
Invitae | RCV000553548 | SCV000623815 | uncertain significance | Hypertrophic cardiomyopathy | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 281 of the TPM1 protein (p.Met281Val). This variant is present in population databases (rs397516394, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of hypertrophic cardiomyopathy (PMID: 27532257, 28356264, 28797094). ClinVar contains an entry for this variant (Variation ID: 43448). 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 tolerated. This variant disrupts the p.Met281 amino acid residue in TPM1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12860912, 18533079, 20965760, 21835320, 22112859, 25524337, 25548289). 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. |