Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003540503 | SCV000772661 | uncertain significance | not provided | 2017-10-01 | 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This sequence change replaces isoleucine with methionine at codon 312 of the POLE protein (p.Ile312Met). 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 with POLE-related disease. |
| Baylor Genetics | RCV000650812 | SCV004203516 | uncertain significance | Colorectal cancer, susceptibility to, 12 | 2023-10-18 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004944063 | SCV005478904 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-07-31 | criteria provided, single submitter | clinical testing | The p.I312M variant (also known as c.936T>G), located in coding exon 10 of the POLE gene, results from a T to G substitution at nucleotide position 936. The isoleucine at codon 312 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |