ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.3355C>T (p.Leu1119Phe)

gnomAD frequency: 0.00001  dbSNP: rs376921543
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002289966 SCV000817736 uncertain significance not provided 2023-09-03 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1119 of the POLE protein (p.Leu1119Phe). This variant is present in population databases (rs376921543, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with POLE-related conditions. ClinVar contains an entry for this variant (Variation ID: 569433). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Sema4, Sema4 RCV002257931 SCV002536807 uncertain significance Hereditary cancer-predisposing syndrome 2021-04-29 criteria provided, single submitter curation
GeneDx RCV002289966 SCV002578560 uncertain significance not provided 2023-10-04 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002257931 SCV002606750 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-14 criteria provided, single submitter clinical testing The p.L1119F variant (also known as c.3355C>T), located in coding exon 27 of the POLE gene, results from a C to T substitution at nucleotide position 3355. The leucine at codon 1119 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.