ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1189G>A (p.Val397Ile) (rs573123885)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000550184 SCV000625510 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-12-23 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 397 of the PMS2 protein (p.Val397Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs573123885, ExAC 0.02%) but has not been reported in the literature in individuals with a PMS2-related disease. 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 summary, this variant is a rare missense change that is not predicted to affect 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 RCV000565558 SCV000663495 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-10 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Color RCV000565558 SCV000691002 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-16 criteria provided, single submitter clinical testing

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