ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.710A>T (p.Gln237Leu) (rs587780061)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212850 SCV000149611 uncertain significance not provided 2018-11-27 criteria provided, single submitter clinical testing This variant is denoted PMS2 c.710A>T at the cDNA level, p.Gln237Leu (Q237L) at the protein level, and results in the change of a Glutamine to a Leucine (CAA>CTA). This variant was identified in an individual with biallelic RNU4ATAC variants and a diagnosis of Roifman syndrome; however, information regarding family history of cancer was not provided (Merico 2015). PMS2 Gln237Leu was not observed at a significant allele frequency in large population cohorts (Lek 2016). PMS2 Gln237Leu is located in 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 Gln237Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000115702 SCV000214919 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-19 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000226619 SCV000285150 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-12-31 criteria provided, single submitter clinical testing This sequence change replaces glutamine with leucine at codon 237 of the PMS2 protein (p.Gln237Leu). The glutamine residue is moderately conserved and there is a moderate physicochemical difference between glutamine 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: 127795). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). 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.
Counsyl RCV000662456 SCV000784934 uncertain significance Hereditary nonpolyposis colorectal cancer type 4 2017-02-07 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765963 SCV000897384 uncertain significance Turcot syndrome; Hereditary nonpolyposis colorectal cancer type 4 2018-10-31 criteria provided, single submitter clinical testing
Color RCV000115702 SCV000909672 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-08 criteria provided, single submitter clinical testing

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