Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003656275 | SCV001213581 | uncertain significance | not provided | 2019-12-06 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with POLE-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with valine at codon 820 of the POLE protein (p.Met820Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. |
| Ambry Genetics | RCV002429635 | SCV002731612 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-23 | criteria provided, single submitter | clinical testing | The p.M820V variant (also known as c.2458A>G), located in coding exon 21 of the POLE gene, results from an A to G substitution at nucleotide position 2458. The methionine at codon 820 is replaced by valine, an amino acid with highly 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. |