Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003656693 | SCV001405199 | uncertain significance | not provided | 2019-07-30 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with POLE-related conditions. This variant is present in population databases (rs770751491, ExAC 0.002%). This sequence change replaces proline with alanine at codon 2020 of the POLE protein (p.Pro2020Ala). The proline residue is moderately conserved and there is a small physicochemical difference between proline and alanine. |
| Ambry Genetics | RCV002356999 | SCV002654630 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-04 | criteria provided, single submitter | clinical testing | The p.P2020A variant (also known as c.6058C>G), located in coding exon 44 of the POLE gene, results from a C to G substitution at nucleotide position 6058. The proline at codon 2020 is replaced by alanine, an amino acid with highly 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. |