Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003541310 | SCV001408441 | uncertain significance | not provided | 2022-08-20 | 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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 961966). This variant has not been reported in the literature in individuals affected with POLE-related conditions. This variant is present in population databases (rs753087966, gnomAD 0.003%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 638 of the POLE protein (p.Asn638Ser). |
| Ambry Genetics | RCV003294117 | SCV003995984 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-11 | criteria provided, single submitter | clinical testing | The p.N638S variant (also known as c.1913A>G), located in coding exon 17 of the POLE gene, results from an A to G substitution at nucleotide position 1913. The asparagine at codon 638 is replaced by serine, 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. |