Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001241075 | SCV001414065 | uncertain significance | Progressive sclerosing poliodystrophy | 2022-10-07 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 134 of the POLG protein (p.Asn134Lys). This variant is present in population databases (rs759939229, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with POLG-related conditions. ClinVar contains an entry for this variant (Variation ID: 966409). 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. Experimental studies have shown that this missense change does not substantially affect POLG function (PMID: 27987238). 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. |
| Fulgent Genetics, |
RCV002499399 | SCV002780170 | 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 | 2021-07-27 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003328664 | SCV004035632 | uncertain significance | not provided | 2023-08-21 | criteria provided, single submitter | clinical testing | Observed in a healthy individual used as a control subject in a study evaluating POLG variants in bipolar disorder. Functional studies indicate comparable enzyme activity between N134K and wild-type (Kasahara et al., 2016); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27987238) |