Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001800950 | SCV001227974 | uncertain significance | not provided | 2023-08-01 | 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. 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 POLE protein function. ClinVar contains an entry for this variant (Variation ID: 857468). This variant has not been reported in the literature in individuals affected with POLE-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 330 of the POLE protein (p.Gly330Val). |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001800950 | SCV002046474 | uncertain significance | not provided | 2020-12-03 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002379586 | SCV002690971 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-22 | criteria provided, single submitter | clinical testing | The p.G330V variant (also known as c.989G>T), located in coding exon 10 of the POLE gene, results from a G to T substitution at nucleotide position 989. The glycine at codon 330 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |