ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1450C>A (p.Pro484Thr) (rs752122569)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000567275 SCV000670832 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-23 criteria provided, single submitter clinical testing Insufficient evidence;In silico models in agreement (benign)
Invitae RCV000629999 SCV000750955 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-01-18 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 484 of the PMS2 protein (p.Pro484Thr). The proline residue is weakly conserved and there is a small physicochemical difference between proline and threonine. This variant is present in population databases (rs752122569, ExAC 0.01%). This variant has been reported in the literature in an individual affected with colorectal cancer, as well as in unaffected control individuals from the Icelandic population (PMID: 24362816, 28466842). ClinVar contains an entry for this variant (Variation ID: 484305). 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 and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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