Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003656184 | SCV001200364 | uncertain significance | not provided | 2019-11-08 | 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 isoleucine with leucine at codon 1925 of the POLE protein (p.Ile1925Leu). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and leucine. |
| Ambry Genetics | RCV002354980 | SCV002653097 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-03 | criteria provided, single submitter | clinical testing | The p.I1925L variant (also known as c.5773A>C), located in coding exon 42 of the POLE gene, results from an A to C substitution at nucleotide position 5773. The isoleucine at codon 1925 is replaced by leucine, 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. |