ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1850C>T (p.Pro617Leu) (rs747785888)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000203758 SCV000260051 uncertain significance Lynch syndrome 2015-08-21 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 617 of the PMS2 protein (p.Pro617Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (no rsID, 0.01%) but has not been reported in the literature. 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. In addition, the leucine 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 rare 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. Therefore, it has been classified as a Variant of Uncertain Significance.

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