Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003656594 | SCV001395196 | uncertain significance | not provided | 2021-09-02 | criteria provided, single submitter | clinical testing | 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. 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. This variant has not been reported in the literature in individuals affected with POLE-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with threonine at codon 2098 of the POLE protein (p.Asn2098Thr). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and threonine. |
| Ambry Genetics | RCV002366005 | SCV002656655 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-30 | criteria provided, single submitter | clinical testing | The p.N2098T variant (also known as c.6293A>C), located in coding exon 45 of the POLE gene, results from an A to C substitution at nucleotide position 6293. The asparagine at codon 2098 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. |