Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001219965 | SCV001391933 | uncertain significance | Progressive sclerosing poliodystrophy | 2023-06-29 | 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. Experimental studies have shown that this missense change does not substantially affect POLG function (PMID: 27987238). 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 not expected to disrupt POLG protein function. ClinVar contains an entry for this variant (Variation ID: 948661). This variant has not been reported in the literature in individuals affected with POLG-related conditions. This variant is present in population databases (rs56410699, gnomAD 0.01%). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 238 of the POLG protein (p.Gln238Arg). |