Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV001004911 | SCV001164415 | uncertain significance | Hypertrophic cardiomyopathy 3 | 2018-12-03 | criteria provided, single submitter | research | The heterozygous p.Glu104Gln variant in TPM1 was identified by our study in one individual with hypertrophic cardiomyopathy. This variant was absent from large population studies. Computational prediction tools and conservation analyses suggest that the variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Glu104Gln variant is uncertain. ACMG/AMP Criteria applied: PM2, PP2, PP3 (Richards 2015). |
Invitae | RCV001860570 | SCV002125514 | uncertain significance | Hypertrophic cardiomyopathy | 2020-12-11 | 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with TPM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 813935). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glutamine at codon 104 of the TPM1 protein (p.Glu104Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. |