ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1682A>C (p.Lys561Thr) (rs876658481)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000217300 SCV000273768 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-13 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000539116 SCV000625548 uncertain significance Hereditary nonpolyposis colon cancer 2019-12-19 criteria provided, single submitter clinical testing This sequence change replaces lysine with threonine at codon 561 of the PMS2 protein (p.Lys561Thr). The lysine residue is weakly conserved and there is a moderate physicochemical difference between lysine and threonine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 230281). 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 threonine 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000217300 SCV001350917 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-29 criteria provided, single submitter clinical testing

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