Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000776457 | SCV000912000 | uncertain significance | Cardiomyopathy | 2023-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with lysine at codon 35 of the TPM1 protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Invitae | RCV001856129 | SCV002174200 | uncertain significance | Hypertrophic cardiomyopathy | 2021-10-18 | 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. This sequence change replaces arginine with lysine at codon 35 of the TPM1 protein (p.Arg35Lys). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and lysine. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 630593). 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). |