Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001226592 | SCV001398913 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-10-12 | 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with PMS2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with methionine at codon 269 of the PMS2 protein (p.Ile269Met). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and methionine. |
| Ambry Genetics | RCV002411835 | SCV002675941 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-23 | criteria provided, single submitter | clinical testing | The p.I269M variant (also known as c.807C>G), located in coding exon 8 of the PMS2 gene, results from a C to G substitution at nucleotide position 807. The isoleucine at codon 269 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. |