ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.797A>T (p.His266Leu)

dbSNP: rs1584765678
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000798998 SCV000938644 uncertain significance Tumor predisposition syndrome 3 2024-12-26 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 266 of the POT1 protein (p.His266Leu). This variant is not present in population databases (gnomAD no frequency). 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: 644988). 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%. Experimental studies have shown that this missense change affects POT1 function (PMID: 31685617). 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 RCV004944165 SCV005477792 uncertain significance Hereditary cancer-predisposing syndrome 2024-06-25 criteria provided, single submitter clinical testing The p.H266L variant (also known as c.797A>T), located in coding exon 6 of the POT1 gene, results from an A to T substitution at nucleotide position 797. The histidine at codon 266 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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.