ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.1282G>A (p.Ala428Thr) (rs150032060)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000459352 SCV000544203 uncertain significance Colorectal cancer, susceptibility to, 12 2019-12-23 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 428 of the POLE protein (p.Ala428Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs150032060, ExAC 0.03%). This variant has been reported in an individual with endometrial cancer (PMID: 25505230). ClinVar contains an entry for this variant (Variation ID: 405877). An experimental study has shown that this variant does not affect the exonuclease activity of the POLE protein (PMID: 25228659). 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.
Ambry Genetics RCV000575925 SCV000671420 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-17 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
GeneDx RCV000602386 SCV000722701 likely benign not specified 2018-02-16 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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