ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.1009C>T (p.Leu337Phe)

dbSNP: rs1795066742
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 RCV001300256 SCV001489392 uncertain significance Tumor predisposition syndrome 3 2021-09-04 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with POT1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with phenylalanine at codon 337 of the POT1 protein (p.Leu337Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine.
Johns Hopkins Genomics, Johns Hopkins University RCV001300256 SCV002570254 uncertain significance Tumor predisposition syndrome 3 2022-05-10 criteria provided, single submitter clinical testing This POT1 variant (rs1795066742) is absent from a large population dataset and has been reported in ClinVar. Two bioinformatic tools queried predict that this substitution would be damaging, while another predicts it would be tolerated. The leucine residue at this position is evolutionarily conserved across most vertebrate species assessed. Bioinformatic analysis predicts that this missense variant would not affect normal exon 13 splicing. This variant has not been reported in the literature in individuals with POT1-related conditions. We consider the clinical significance of c.1009C>T to be uncertain at this time.
GeneDx RCV002285473 SCV002575991 uncertain significance not provided 2022-03-21 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002451667 SCV002739892 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-04 criteria provided, single submitter clinical testing The p.L337F variant (also known as c.1009C>T), located in coding exon 9 of the POT1 gene, results from a C to T substitution at nucleotide position 1009. The leucine at codon 337 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly 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.

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.