ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1186A>G (p.Met396Val) (rs863224675)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000200769 SCV000254594 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-07-02 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 396 of the PMS2 protein (p.Met396Val). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and valine. 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: 216448). 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 valine 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.
Ambry Genetics RCV000220813 SCV000273471 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-25 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Color RCV000220813 SCV001353139 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-28 criteria provided, single submitter clinical testing

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