Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Blueprint Genetics | RCV000208266 | SCV000264273 | uncertain significance | Sudden cardiac death | 2015-05-04 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001853316 | SCV002249059 | uncertain significance | Progressive familial heart block type IB | 2022-11-21 | 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. 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 glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 222853). This variant has not been reported in the literature in individuals affected with TRPM4-related conditions. This variant is present in population databases (rs547541099, gnomAD 0.008%). This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 609 of the TRPM4 protein (p.Ala609Gly). |
Ambry Genetics | RCV002408908 | SCV002713142 | uncertain significance | Cardiovascular phenotype | 2023-11-21 | criteria provided, single submitter | clinical testing | The p.A609G variant (also known as c.1826C>G), located in coding exon 13 of the TRPM4 gene, results from a C to G substitution at nucleotide position 1826. The alanine at codon 609 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and glycine is the reference amino acid in other 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. |