ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.6442T>C (p.Cys2148Arg)

dbSNP: rs2041835652
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
Invitae RCV002264173 SCV001229663 uncertain significance not provided 2023-01-17 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt POLE protein function. ClinVar contains an entry for this variant (Variation ID: 858788). This variant has not been reported in the literature in individuals affected with POLE-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 2148 of the POLE protein (p.Cys2148Arg).
CeGaT Center for Human Genetics Tuebingen RCV002264173 SCV002545088 uncertain significance not provided 2022-05-01 criteria provided, single submitter clinical testing POLE: PM2
Ambry Genetics RCV002365753 SCV002659614 uncertain significance Hereditary cancer-predisposing syndrome 2021-07-19 criteria provided, single submitter clinical testing The p.C2148R variant (also known as c.6442T>C), located in coding exon 46 of the POLE gene, results from a T to C substitution at nucleotide position 6442. The cysteine at codon 2148 is replaced by arginine, an amino acid with highly dissimilar 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.
GeneDx RCV002264173 SCV004169244 uncertain significance not provided 2023-04-24 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

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.