Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002926893 | SCV003256175 | uncertain significance | Colorectal cancer, susceptibility to, 12 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with methionine at codon 387 of the POLE protein (p.Ile387Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with POLE-related conditions. 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 C0"). 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. |
| Ambry Genetics | RCV003167930 | SCV003911805 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-24 | criteria provided, single submitter | clinical testing | The p.I387M variant (also known as c.1161A>G), located in coding exon 12 of the POLE gene, results from an A to G substitution at nucleotide position 1161. The isoleucine at codon 387 is replaced by methionine, 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. |