Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001875110 | SCV002142571 | uncertain significance | Progressive sclerosing poliodystrophy | 2023-04-10 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1373283). 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. This variant has not been reported in the literature in individuals affected with POLG-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 585 of the POLG protein (p.Trp585Arg). |
Ambry Genetics | RCV004040588 | SCV005007097 | uncertain significance | Inborn genetic diseases | 2023-12-21 | criteria provided, single submitter | clinical testing | The c.1753T>A (p.W585R) alteration is located in exon 10 (coding exon 9) of the POLG gene. This alteration results from a T to A substitution at nucleotide position 1753, causing the tryptophan (W) at amino acid position 585 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |