ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.949C>A (p.Gln317Lys) (rs143277125)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483849 SCV000566055 uncertain significance not provided 2018-03-08 criteria provided, single submitter clinical testing This variant is denoted PMS2 c.949C>A at the cDNA level, p.Gln317Lys (Q317K) at the protein level, and results in the change of a Glutamine to a Lysine (CAG>AAG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PMS2 Gln317Lys was not observed at a significant allele frequency in large population cohorts (Lek 2016). PMS2 Gln317Lys is located within 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 Gln317Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000538453 SCV000625711 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2018-03-28 criteria provided, single submitter clinical testing This sequence change replaces glutamine with lysine at codon 317 of the PMS2 protein (p.Gln317Lys). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and lysine. This variant is present in population databases (rs143277125, ExAC 0.01%). This variant has not been reported in the literature in individuals with PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 418758). 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 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.
Ambry Genetics RCV000566189 SCV000663475 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-02 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Color RCV000566189 SCV000686258 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-16 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765958 SCV000897379 uncertain significance Turcot syndrome; Hereditary nonpolyposis colorectal cancer type 4 2018-10-31 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000483849 SCV001134618 uncertain significance not provided 2019-01-09 criteria provided, single submitter clinical testing

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