ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.641T>G (p.Val214Gly) (rs864622706)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000206866 SCV000261967 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-07-01 criteria provided, single submitter clinical testing This sequence change replaces valine with glycine at codon 214 of the PMS2 protein (p.Val214Gly). The valine residue is moderately conserved and there is a moderate physicochemical difference between valine and glycine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 220964). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000759926 SCV000565387 uncertain significance not provided 2018-10-11 criteria provided, single submitter clinical testing This variant is denoted PMS2 c.641T>G at the cDNA level, p.Val214Gly (V214G) at the protein level, and results in the change of a Valine to a Glycine (GTG>GGG). This variant has been reported in at least one individual with mismatch repair-deficient colorectal cancer (Le 2017). PMS2 Val214Gly was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the ATPase domain (Guarne 2001). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether PMS2 Val214Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000584176 SCV000691093 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-13 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759926 SCV000889636 uncertain significance not provided 2018-03-22 criteria provided, single submitter clinical testing

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