Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002450474 | SCV002732716 | uncertain significance | Inborn genetic diseases | 2018-06-12 | criteria provided, single submitter | clinical testing | The p.W815C variant (also known as c.2445G>C), located in coding exon 14 of the POLG gene, results from a G to C substitution at nucleotide position 2445. The tryptophan at codon 815 is replaced by cysteine, an amino acid with highly 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. |
| Labcorp Genetics |
RCV003514583 | SCV004278711 | uncertain significance | Progressive sclerosing poliodystrophy | 2023-07-19 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt POLG protein function. ClinVar contains an entry for this variant (Variation ID: 1791385). This variant has not been reported in the literature in individuals affected with POLG-related conditions. This variant is present in population databases (rs770829807, gnomAD 0.003%). This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 815 of the POLG protein (p.Trp815Cys). |