ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.535T>C (p.Phe179Leu)

gnomAD frequency: 0.00001  dbSNP: rs775453323
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 RCV001976371 SCV002264742 uncertain significance Tumor predisposition syndrome 3 2025-01-21 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 179 of the POT1 protein (p.Phe179Leu). This variant is present in population databases (rs775453323, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with POT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1475606). 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 POT1 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.
Ambry Genetics RCV002344151 SCV002646374 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-20 criteria provided, single submitter clinical testing The p.F179L variant (also known as c.535T>C), located in coding exon 4 of the POT1 gene, results from a T to C substitution at nucleotide position 535. The phenylalanine at codon 179 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. 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.
GeneDx RCV004797980 SCV005420196 uncertain significance not provided 2024-05-31 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; This variant is associated with the following publications: (PMID: 28393830)

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.