Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000557681 | SCV000625581 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2017-03-20 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with glutamic acid at codon 685 of the PMS2 protein (p.Gly685Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is absent in the population databases (ExAC) and has not been reported in the literature in individuals with a PMS2-related disease. However, the frequency data is considered unreliable due to the presence of a pseudogene that has strong homology to this region. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. 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 disruptive, but these predictions have not been confirmed by published functional studies. |