Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001895862 | SCV002155621 | uncertain significance | Progressive familial heart block type IB | 2022-07-29 | 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 glutamine 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: 1384264). This variant has not been reported in the literature in individuals affected with TRPM4-related conditions. This variant is present in population databases (rs747502300, gnomAD 0.002%). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 218 of the TRPM4 protein (p.Glu218Gln). |
| Ambry Genetics | RCV004041318 | SCV004971115 | uncertain significance | Cardiovascular phenotype | 2023-12-22 | criteria provided, single submitter | clinical testing | The c.652G>C (p.E218Q) alteration is located in exon 6 (coding exon 6) of the TRPM4 gene. This alteration results from a G to C substitution at nucleotide position 652, causing the glutamic acid (E) at amino acid position 218 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |