ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1578C>G (p.Asp526Glu) (rs63750236)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000199308 SCV000254602 uncertain significance Lynch syndrome 2015-04-22 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glutamic acid at codon 526 of the PMS2 protein (p.Asp526Glu). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant has not been published in the literature and is not present in population databases. General algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) and an algorithm developed specifically for mismatch repair genes including the PMS2 (PMID: 22949387) all suggest that this missense change is likely to be tolerated, although these predictions have not been confirmed by published functional studies. 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.
Color RCV000582571 SCV000691029 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-24 criteria provided, single submitter clinical testing

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