ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.1019A>T (p.Glu340Val) (rs895236041)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507732 SCV000601969 uncertain significance not specified 2017-06-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV001009694 SCV001169792 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-24 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV001068670 SCV001233795 uncertain significance Colorectal cancer, susceptibility to, 12 2019-11-25 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with valine at codon 340 of the POLE protein (p.Glu340Val). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with POLE-related conditions. ClinVar contains an entry for this variant (Variation ID: 439260). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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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