Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics | RCV002475510 | SCV002770700 | uncertain significance | not provided | 2021-06-15 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003514593 | SCV004296588 | likely pathogenic | Progressive sclerosing poliodystrophy | 2023-09-13 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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: 1807553). This missense change has been observed in individuals with autosomal recessive POLG-related conditions (PMID: 27290639, 30423451, 33486010). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 880 of the POLG protein (p.Ala880Asp). |