ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.4738C>T (p.Arg1580Trp) (rs192908615)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000462872 SCV000544063 uncertain significance Colorectal cancer, susceptibility to, 12 2019-12-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 1580 of the POLE protein (p.Arg1580Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs192908615, 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: 405742). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985983 SCV001134733 uncertain significance not provided 2018-12-27 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000985983 SCV001148884 uncertain significance not provided 2019-03-01 criteria provided, single submitter clinical testing

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