ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.863C>G (p.Ala288Gly) (rs771619667)

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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 RCV000507034 SCV000602103 uncertain significance not specified 2017-06-09 criteria provided, single submitter clinical testing
Ambry Genetics RCV000574444 SCV000671503 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-30 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000690986 SCV000818720 uncertain significance Colorectal cancer, susceptibility to, 12 2019-09-13 criteria provided, single submitter clinical testing This sequence change replaces alanine with glycine at codon 288 of the POLE protein (p.Ala288Gly). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and glycine. This variant is present in population databases (rs771619667, ExAC 0.01%). This variant has not been reported in the literature in individuals with POLE-related disease. ClinVar contains an entry for this variant (Variation ID: 439282). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a 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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