Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Wong Mito Lab, |
RCV000758488 | SCV000887204 | uncertain significance | Progressive sclerosing poliodystrophy | 2018-10-01 | criteria provided, single submitter | clinical testing | The NM_002693.2:c.824G>A (NP_002684.1:p.Arg275Gln) [GRCH38: NC_000015.10:g.89330112C>T] variant in POLG gene is interpretated to be a Uncertain Significance based on ACMG guidelines (PMID: 25741868). This variant meets the following evidence codes reported in the ACMG-guideline. PP3:Computational evidence/predictors indicate the variant has deleterious effect on POLG structure, function, or protein-protein interaction. Based on the evidence criteria codes applied, the variant is suggested to be Uncertain Significance. |
Fulgent Genetics, |
RCV002485967 | SCV002779216 | uncertain significance | Progressive sclerosing poliodystrophy; Mitochondrial DNA depletion syndrome 1; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1; Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis; Mitochondrial DNA depletion syndrome 4b | 2022-03-17 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000758488 | SCV004205898 | likely pathogenic | Progressive sclerosing poliodystrophy | 2023-06-13 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000758488 | SCV004296599 | pathogenic | Progressive sclerosing poliodystrophy | 2023-04-13 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects POLG function (PMID: 26095671). 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: 619447). This missense change has been observed in individual(s) with autosomal recessive POLG-related disorders (PMID: 20837861, 30552426). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 275 of the POLG protein (p.Arg275Gln). |