Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000800286 | SCV000939991 | uncertain significance | Progressive familial heart block type IB | 2024-01-16 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 763 of the TRPM4 protein (p.Cys763Trp). This variant is present in population databases (rs200760537, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with TRPM4-related conditions. ClinVar contains an entry for this variant (Variation ID: 646069). 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. 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 | RCV002442654 | SCV002736305 | uncertain significance | Cardiovascular phenotype | 2023-09-23 | criteria provided, single submitter | clinical testing | The p.C763W variant (also known as c.2289C>G), located in coding exon 17 of the TRPM4 gene, results from a C to G substitution at nucleotide position 2289. The cysteine at codon 763 is replaced by tryptophan, an amino acid with highly dissimilar properties. This amino acid position is poorly 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. |
Dept of Medical Biology, |
RCV003318385 | SCV004022009 | uncertain significance | Long QT syndrome | 2024-01-08 | criteria provided, single submitter | research | Criteria: BP4 |
Breakthrough Genomics, |
RCV004693287 | SCV005194738 | uncertain significance | not provided | criteria provided, single submitter | not provided |