ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.94G>T (p.Val32Leu) (rs977251189)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000473006 SCV000551997 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-11-05 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 32 of the PMS2 protein (p.Val32Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. 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. ClinVar contains an entry for this variant (Variation ID: 411049). 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: "Benign"; 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.
GeneDx RCV000485503 SCV000568131 uncertain significance not provided 2018-06-01 criteria provided, single submitter clinical testing This variant is denoted PMS2 c.94G>T at the cDNA level, p.Val32Leu (V32L) at the protein level, and results in the change of a Valine to a Leucine (GTA>TTA). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. PMS2 Val32Leu was not observed in large population cohorts (Lek 2016). This variant is located in the ATPase domain (Guarne 2001, Fukui 2011). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether PMS2 Val32Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000562693 SCV000670788 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-28 criteria provided, single submitter clinical testing Insufficient evidence;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Color RCV000562693 SCV000686259 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-26 criteria provided, single submitter clinical testing

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