Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001757040 | SCV001996559 | uncertain significance | not provided | 2019-11-17 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function |
Labcorp Genetics |
RCV003626683 | SCV004481937 | uncertain significance | Progressive sclerosing poliodystrophy | 2023-01-19 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). 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 not expected to disrupt POLG protein function. ClinVar contains an entry for this variant (Variation ID: 1309972). This variant has not been reported in the literature in individuals affected with POLG-related conditions. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 38 of the POLG protein (p.Gly38Arg). |