Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001931568 | SCV002199783 | uncertain significance | Hypertrophic cardiomyopathy | 2021-06-28 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with TPM1-related conditions. 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 is present in population databases (rs774903903, ExAC 0.01%). This sequence change replaces isoleucine with valine at codon 171 of the TPM1 protein (p.Ile171Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. |
Ambry Genetics | RCV002344075 | SCV002646506 | uncertain significance | Cardiovascular phenotype | 2021-11-03 | criteria provided, single submitter | clinical testing | The p.I171V variant (also known as c.511A>G), located in coding exon 5 of the TPM1 gene, results from an A to G substitution at nucleotide position 511. The isoleucine at codon 171 is replaced by valine, an amino acid with highly similar properties. This variant was observed in one control individual from a hypertrophic cardiomyopathy (HCM) study; however, clinical details were limited (Kapplinger JD et al. J Cardiovasc Transl Res, 2014 Apr;7:347-61). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002484623 | SCV002783946 | uncertain significance | Hypertrophic cardiomyopathy 3; Dilated cardiomyopathy 1Y | 2021-07-30 | criteria provided, single submitter | clinical testing |