Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000811158 | SCV000951410 | uncertain significance | Progressive sclerosing poliodystrophy | 2023-09-20 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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: 655061). This variant has not been reported in the literature in individuals affected with POLG-related conditions. This variant is present in population databases (rs752073900, gnomAD 0.02%). This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 653 of the POLG protein (p.Glu653Val). |
| Gene |
RCV001766695 | SCV001990899 | uncertain significance | not provided | 2019-04-02 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function |