ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.5035C>T (p.Arg1679Cys)

gnomAD frequency: 0.00001  dbSNP: rs768244569
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001556080 SCV000544117 uncertain significance not provided 2025-01-07 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1679 of the POLE protein (p.Arg1679Cys). This variant is present in population databases (rs768244569, gnomAD 0.02%). 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: 405795). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt POLE protein function with a negative predictive value of 80%. 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.
Fulgent Genetics, Fulgent Genetics RCV000765049 SCV000896246 uncertain significance Colorectal cancer, susceptibility to, 12; Facial dysmorphism-immunodeficiency-livedo-short stature syndrome 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV001556080 SCV001777595 uncertain significance not provided 2023-11-03 criteria provided, single submitter clinical testing 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; This variant is associated with the following publications: (PMID: 29056344)
Ambry Genetics RCV002339128 SCV002644367 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-03 criteria provided, single submitter clinical testing The p.R1679C variant (also known as c.5035C>T), located in coding exon 38 of the POLE gene, results from a C to T substitution at nucleotide position 5035. The arginine at codon 1679 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002465655 SCV002760614 uncertain significance not specified 2024-07-31 criteria provided, single submitter clinical testing

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.