Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002036132 | SCV002313160 | uncertain significance | Progressive familial heart block type IB | 2021-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with leucine at codon 233 of the TRPM4 protein (p.Phe233Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with TRPM4-related conditions. This variant is present in population databases (rs770448797, ExAC 0.01%). |
| Ambry Genetics | RCV003161304 | SCV003858014 | uncertain significance | Cardiovascular phenotype | 2022-12-12 | criteria provided, single submitter | clinical testing | The p.F233L variant (also known as c.697T>C), located in coding exon 6 of the TRPM4 gene, results from a T to C substitution at nucleotide position 697. The phenylalanine at codon 233 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |