ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.4223A>G (p.Gln1408Arg)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003658395 SCV003249480 uncertain significance not provided 2021-12-15 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with POLE-related conditions. This variant is present in population databases (rs769798010, gnomAD 0.003%). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 1408 of the POLE protein (p.Gln1408Arg).
Ambry Genetics RCV004946095 SCV005478983 uncertain significance Hereditary cancer-predisposing syndrome 2024-07-15 criteria provided, single submitter clinical testing The p.Q1408R variant (also known as c.4223A>G), located in coding exon 33 of the POLE gene, results from an A to G substitution at nucleotide position 4223. The glutamine at codon 1408 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
GeneDx RCV003658395 SCV005690486 uncertain significance not provided 2024-08-08 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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.