ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.1309G>A (p.Val437Met) (rs115047349)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000239213 SCV000297203 uncertain significance not specified 2015-11-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV000569269 SCV000671482 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-23 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000650917 SCV000772766 uncertain significance Colorectal cancer, susceptibility to, 12 2018-07-08 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 437 of the POLE protein (p.Val437Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs115047349, 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: 252659). 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.
Counsyl RCV000650917 SCV000786466 uncertain significance Colorectal cancer, susceptibility to, 12 2018-05-30 criteria provided, single submitter clinical testing

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