Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001923652 | SCV002196717 | uncertain significance | Progressive familial heart block type IB | 2023-06-27 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1421042). This variant has not been reported in the literature in individuals affected with TRPM4-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1075 of the TRPM4 protein (p.Leu1075Arg). |
| Ambry Genetics | RCV002324337 | SCV002609882 | uncertain significance | Cardiovascular phenotype | 2022-03-31 | criteria provided, single submitter | clinical testing | The p.L1075R variant (also known as c.3224T>G), located in coding exon 21 of the TRPM4 gene, results from a T to G substitution at nucleotide position 3224. The leucine at codon 1075 is replaced by arginine, an amino acid with dissimilar properties. 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. |
| Dept of Medical Biology, |
RCV003318408 | SCV004022032 | uncertain significance | Long QT syndrome | 2024-01-08 | criteria provided, single submitter | research | Criteria: PM2, PP3 |