Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003117600 | SCV000949748 | uncertain significance | not provided | 2023-04-25 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 653768). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 269 of the POLE protein (p.Pro269Ala). This variant is present in population databases (rs757438555, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with POLE-related conditions. |
| Ambry Genetics | RCV001027123 | SCV001189629 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-29 | criteria provided, single submitter | clinical testing | The p.P269A variant (also known as c.805C>G), located in coding exon 9 of the POLE gene, results from a C to G substitution at nucleotide position 805. The proline at codon 269 is replaced by alanine, an amino acid with highly 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. |
| Gene |
RCV003117600 | SCV003798922 | uncertain significance | not provided | 2023-02-03 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 20951805) |
| Baylor Genetics | RCV004569659 | SCV005056546 | uncertain significance | Colorectal cancer, susceptibility to, 12 | 2024-02-02 | criteria provided, single submitter | clinical testing |