ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.2759C>T (p.Thr920Ile)

dbSNP: rs899872545
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001760197 SCV001388525 uncertain significance not provided 2019-04-23 criteria provided, single submitter clinical testing 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. This variant has not been reported in the literature in individuals with POLE-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 920 of the POLE protein (p.Thr920Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine.
GeneDx RCV001760197 SCV001999305 uncertain significance not provided 2019-10-15 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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