ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.6135C>T (p.Pro2045=) (rs368662693)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000439221 SCV000522133 likely benign not specified 2017-08-23 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 RCV000472140 SCV000544196 uncertain significance Colorectal cancer, susceptibility to, 12 2019-12-23 criteria provided, single submitter clinical testing This sequence change affects codon 2045 of the POLE mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the POLE protein. This variant is present in population databases (rs368662693, ExAC 0.06%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with POLE-related disease. ClinVar contains an entry for this variant (Variation ID: 382254). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, 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.
Ambry Genetics RCV000565715 SCV000671490 likely benign Hereditary cancer-predisposing syndrome 2016-02-09 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000439221 SCV000712575 uncertain significance not specified 2016-11-18 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Pro2045Pro va riant in POLE has not been previously reported in individuals with colorectal ca ncer but has been identified in 5/8596 of East Asian chromosomes by the Exome Ag gregation Consortium (ExAC,; dbSNP rs368662693). This variant is located in the last three bases of the exon, which is part of th e 5? splice region. Computational tools do not suggest an impact to splicing. Ho wever, this information is not predictive enough to rule out pathogenicity. In s ummary, the clinical significance of the p.Pro2045Pro variant is uncertain altho ugh it is suspected to be more likely benign.
True Health Diagnostics RCV000565715 SCV000788188 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-29 no assertion criteria provided clinical testing

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