Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001324766 | SCV001515731 | uncertain significance | Progressive familial heart block type IB | 2021-02-09 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with isoleucine at codon 936 of the TRPM4 protein (p.Phe936Ile). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TRPM4-related conditions. 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"). 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 | RCV003294296 | SCV003998394 | uncertain significance | Cardiovascular phenotype | 2023-05-22 | criteria provided, single submitter | clinical testing | The p.F936I variant (also known as c.2806T>A), located in coding exon 19 of the TRPM4 gene, results from a T to A substitution at nucleotide position 2806. The phenylalanine at codon 936 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |