Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003656529 | SCV001385078 | uncertain significance | not provided | 2021-10-01 | 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. This variant has not been reported in the literature in individuals affected with POLE-related conditions. This variant is present in population databases (rs752475451, ExAC 0.002%). This sequence change replaces glutamine with arginine at codon 1507 of the POLE protein (p.Gln1507Arg). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and arginine. |
| Ambry Genetics | RCV002339553 | SCV002638481 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-03 | criteria provided, single submitter | clinical testing | The p.Q1507R variant (also known as c.4520A>G), located in coding exon 35 of the POLE gene, results from an A to G substitution at nucleotide position 4520. The glutamine at codon 1507 is replaced by arginine, 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. |