Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genomic Diagnostic Laboratory, |
RCV000203005 | SCV000257930 | uncertain significance | not specified | 2015-06-16 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002515497 | SCV003497907 | uncertain significance | Progressive sclerosing poliodystrophy | 2022-09-14 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 218616). This variant has not been reported in the literature in individuals affected with POLG-related conditions. This variant is present in population databases (rs778531134, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 276 of the POLG protein (p.Ala276Thr). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on POLG protein function. 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. |