Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001121336 | SCV001279929 | uncertain significance | POLG-Related Spectrum Disorders | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Labcorp Genetics |
RCV001856597 | SCV002282163 | likely pathogenic | Progressive sclerosing poliodystrophy | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 1051 of the POLG protein (p.Gly1051Trp). This variant is present in population databases (rs121918049, gnomAD 0.01%). 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: 888159). 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 with a positive predictive value of 95%. This variant disrupts the p.Gly1051 amino acid residue in POLG. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14745080, 28130605, 30818899). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| Genetics and Molecular Pathology, |
RCV002466625 | SCV002761692 | uncertain significance | Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 | 2022-05-27 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002491375 | SCV002790549 | 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 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003322852 | SCV004028306 | uncertain significance | not provided | 2023-02-17 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; 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 |