Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003541156 | SCV001387442 | uncertain significance | not provided | 2022-09-15 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 945125). 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 serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 382 of the POLE protein (p.Ser382Thr). 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 not expected to disrupt POLE protein function. |
| Ambry Genetics | RCV002451473 | SCV002613632 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-10-29 | criteria provided, single submitter | clinical testing | The p.S382T variant (also known as c.1145G>C), located in coding exon 12 of the POLE gene, results from a G to C substitution at nucleotide position 1145. The serine at codon 382 is replaced by threonine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |