Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001018723 | SCV001179993 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-09 | criteria provided, single submitter | clinical testing | The p.V302I variant (also known as c.904G>A) is located in coding exon 9 of the PMS2 gene. The valine at codon 302 is replaced by isoleucine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 9. This amino acid position is highly conserved in available vertebrate species. 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. |
| Invitae | RCV003758979 | SCV004375982 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 302 of the PMS2 protein (p.Val302Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 822944). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |