Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000521387 | SCV000619758 | uncertain significance | not provided | 2017-08-09 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the TPM1 gene. The Q9L variant has not been published as pathogenic or been reported as benign to our knowledge. The Q9L variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Q9L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Furthermore, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, no missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with HCM (Stenson et al., 2014). |
Invitae | RCV001857996 | SCV002212127 | uncertain significance | Hypertrophic cardiomyopathy | 2021-09-09 | criteria provided, single submitter | clinical testing | 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. 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: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 451106). This variant has not been reported in the literature in individuals affected with TPM1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with leucine at codon 9 of the TPM1 protein (p.Gln9Leu). The glutamine residue is moderately conserved and there is a moderate physicochemical difference between glutamine and leucine. |