ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.983A>G (p.Tyr328Cys)

gnomAD frequency: 0.00001  dbSNP: rs1339375099
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 RCV001284696 SCV000653498 uncertain significance not provided 2025-01-08 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 328 of the POLE protein (p.Tyr328Cys). This variant is not present in population databases (gnomAD no frequency). 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: 473847). 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 expected to disrupt POLE protein function with a positive 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.
Ambry Genetics RCV000568842 SCV000676229 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-23 criteria provided, single submitter clinical testing The p.Y328C variant (also known as c.983A>G), located in coding exon 10 of the POLE gene, results from an A to G substitution at nucleotide position 983. The tyrosine at codon 328 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284696 SCV001470626 uncertain significance not provided 2020-07-30 criteria provided, single submitter clinical testing
GeneDx RCV001284696 SCV003762013 uncertain significance not provided 2023-01-24 criteria provided, single submitter clinical testing Not observed 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; This variant is associated with the following publications: (PMID: 20951805)

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.