Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001010507 | SCV001170718 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-03-12 | criteria provided, single submitter | clinical testing | The p.S415G variant (also known as c.1243A>G), located in coding exon 13 of the POLE gene, results from an A to G substitution at nucleotide position 1243. The serine at codon 415 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly 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. |
| Invitae | RCV003541269 | SCV001509485 | 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. This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 415 of the POLE protein (p.Ser415Gly). This variant is not present in population databases (gnomAD no frequency). 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: 818680). This variant has not been reported in the literature in individuals affected with POLE-related conditions. |