ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.2146A>G (p.Thr716Ala) (rs772637411)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000536358 SCV000625586 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2017-03-14 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 716 of the PMS2 protein (p.Thr716Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in the population databases (rs772637411, 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001014570 SCV001175294 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-28 criteria provided, single submitter clinical testing Insufficient evidence

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