Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001958185 | SCV002226974 | uncertain significance | Progressive familial heart block type IB | 2022-06-22 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with TRPM4-related conditions. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 632 of the TRPM4 protein (p.Arg632Cys). This variant is not present in population databases (gnomAD no frequency). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
| Ambry Genetics | RCV004043711 | SCV003892513 | uncertain significance | Cardiovascular phenotype | 2023-04-17 | criteria provided, single submitter | clinical testing | The p.R632C variant (also known as c.1894C>T), located in coding exon 14 of the TRPM4 gene, results from a C to T substitution at nucleotide position 1894. The arginine at codon 632 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |