ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.4450A>C (p.Ile1484Leu) (rs772734618)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000765056 SCV000896253 uncertain significance Colorectal cancer, susceptibility to, 12; Facial dysmorphism, immunodeficiency, livedo, and short stature 2018-10-31 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000502970 SCV000596498 uncertain significance not specified 2017-01-13 criteria provided, single submitter clinical testing
Invitae RCV000230629 SCV000289379 uncertain significance Colorectal cancer, susceptibility to, 12 2018-06-19 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with leucine at codon 1484 of the POLE protein (p.Ile1484Leu). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and leucine. This variant is present in population databases (rs772734618, ExAC 0.002%). This variant has not been reported in the literature in individuals with POLE-related disease. ClinVar contains an entry for this variant (Variation ID: 240515). 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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