Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003656260 | SCV001211801 | uncertain significance | not provided | 2023-12-17 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1093 of the POLE protein (p.Ala1093Thr). This variant is present in population databases (rs757323968, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with POLE-related conditions. ClinVar contains an entry for this variant (Variation ID: 844862). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 | RCV002320271 | SCV002611078 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-19 | criteria provided, single submitter | clinical testing | The p.A1093T variant (also known as c.3277G>A), located in coding exon 27 of the POLE gene, results from a G to A substitution at nucleotide position 3277. The alanine at codon 1093 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. 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. |