ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.825A>T (p.Gln275His) (rs876659736)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000708993 SCV000838190 uncertain significance Lynch syndrome 2018-07-02 criteria provided, single submitter clinical testing
Mendelics RCV000987842 SCV001137314 uncertain significance Hereditary nonpolyposis colorectal cancer type 4 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV001046149 SCV001210038 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-07-31 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 275 of the PMS2 protein (p.Gln275His). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with colorectal cancer (PMID: 30256826). ClinVar contains an entry for this variant (Variation ID: 584683). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
Color RCV001188465 SCV001355533 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-10 criteria provided, single submitter clinical testing

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