ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.2245A>G (p.Asn749Asp) (rs878854045)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000229194 SCV000285111 uncertain significance Lynch syndrome 2015-11-24 criteria provided, single submitter clinical testing This sequence change replaces asparagine with aspartic acid at codon 749 of the PMS2 protein (p.Asn749Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is not present in the population databases (ExAC no frequency) and has not been reported in the literature in individuals with a PMS2-related disease. However, frequency data for variants in this region of PMS2 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). In summary, this 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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