Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003656618 | SCV001399933 | uncertain significance | not provided | 2021-03-18 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 methionine at codon 211 of the POLE protein (p.Ile211Met). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and methionine. |
| Ambry Genetics | RCV002366020 | SCV002661136 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-21 | criteria provided, single submitter | clinical testing | The p.I211M variant (also known as c.633A>G), located in coding exon 7 of the POLE gene, results from an A to G substitution at nucleotide position 633. The isoleucine at codon 211 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. |