ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.6818C>T (p.Thr2273Ile) (rs779145729)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506821 SCV000602094 uncertain significance not specified 2017-06-08 criteria provided, single submitter clinical testing
Invitae RCV000650835 SCV000772684 uncertain significance Colorectal cancer, susceptibility to, 12 2019-11-29 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 2273 of the POLE protein (p.Thr2273Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs779145729, ExAC 0.03%). This variant has not been reported in the literature in individuals with POLE-related disease. ClinVar contains an entry for this variant (Variation ID: 439280). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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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