Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000821967 | SCV000962743 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2018-12-06 | 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 sequence change replaces methionine with lysine at codon 797 of the PMS2 protein (p.Met797Lys). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and lysine. The frequency data for this variant in the population databases (ExAC) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. |