Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000700105 | SCV000828846 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2018-03-31 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with leucine at codon 555 of the PMS2 protein (p.Gln555Leu). The glutamine residue is weakly conserved and there is a moderate physicochemical difference between glutamine and leucine. This variant is present in population databases (rs745836140, ExAC 0.01%). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |