ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.3270G>A (p.Thr1090=) (rs758258927)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569530 SCV000671565 likely benign Hereditary cancer-predisposing syndrome 2017-05-17 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
GeneDx RCV000600656 SCV000718464 likely benign not specified 2018-03-02 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.
Invitae RCV000703492 SCV000832395 uncertain significance Colorectal cancer, susceptibility to, 12 2019-12-09 criteria provided, single submitter clinical testing This sequence change affects codon 1090 of the POLE mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the POLE protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with POLE-related disease. ClinVar contains an entry for this variant (Variation ID: 484504). 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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