ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.2054G>A (p.Gly685Glu) (rs1554295923)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000557681 SCV000625581 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2017-04-07 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 685 of the PMS2 protein (p.Gly685Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is absent in the population databases (ExAC) and has not been reported in the literature in individuals with a PMS2-related disease. However, the frequency data is considered unreliable due to the presence of a pseudogene that has strong homology to this region. 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 disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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