Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000701484 | SCV000830286 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-09-14 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with threonine at codon 299 of the PMS2 protein (p.Pro299Thr). The proline residue is moderately conserved and there is a small physicochemical difference between proline and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PMS2-related disease. 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: "Tolerated"; 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 | RCV001018544 | SCV001179796 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-23 | criteria provided, single submitter | clinical testing | Insufficient evidence |