Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001902331 | SCV002128423 | uncertain significance | Progressive sclerosing poliodystrophy | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 678 of the POLG protein (p.Glu678Gly). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 1363555). 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. |
| Ambry Genetics | RCV004039847 | SCV005007100 | uncertain significance | Inborn genetic diseases | 2023-12-06 | criteria provided, single submitter | clinical testing | The c.2033A>G (p.E678G) alteration is located in exon 11 (coding exon 10) of the POLG gene. This alteration results from a A to G substitution at nucleotide position 2033, causing the glutamic acid (E) at amino acid position 678 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |