Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003656412 | SCV001233726 | uncertain significance | not provided | 2023-09-12 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 861975). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1472 of the POLE protein (p.Ser1472Pro). This variant is present in population databases (rs767361716, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with POLE-related conditions. 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. 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 | RCV002327357 | SCV002629167 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-19 | criteria provided, single submitter | clinical testing | The p.S1472P variant (also known as c.4414T>C), located in coding exon 34 of the POLE gene, results from a T to C substitution at nucleotide position 4414. The serine at codon 1472 is replaced by proline, an amino acid with similar 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. |