ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.542A>T (p.Tyr181Phe) (rs863224681)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000196226 SCV000254615 uncertain significance Lynch syndrome 2015-04-24 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with phenylalanine at codon 181 of the PMS2 protein (p.Tyr181Phe). The tyrosine residue is weakly conserved and there is a small physicochemical difference between tyrosine and phenylalanine. This variant has not been published in the literature and is not present in population databases. 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 tolerated, but these predictions have not been confirmed by published functional studies. The phenylalanine amino acid residue is found in multiple mammalian species, also suggesting that this missense change does not adversely affect protein function. In summary, this is a novel missense change that is not predicted to affect protein function or cause disease. However, the evidence is insufficient at this time to prove that conclusively. It has been classified as a Variant of Uncertain Significance.
GeneKor MSA RCV000708734 SCV000822135 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing

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