ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.1071dup (p.Gln358fs) (rs750470470)

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
GeneDx RCV000657444 SCV000779179 likely pathogenic not provided 2018-01-08 criteria provided, single submitter clinical testing This duplication of one nucleotide in POT1 is denoted c.1071dupT at the cDNA level and p.Gln358SerfsX13 (Q358SfsX13) at the protein level. The normal sequence, with the base that is duplicated in brackets, is CTCC[dupT]CAAC. The duplication causes a frameshift which changes a Glutamine to a Serine at codon 358, and creates a premature stop codon at position 13 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. POT1 c.1071dupT was observed in two affected members of a kindred with familial chronic lymphocytic leukemia (Speedy 2016). Based on currently available evidence, we consider this duplication to be a likely pathogenic variant.
Invitae RCV000652206 SCV000774074 uncertain significance Melanoma, cutaneous malignant, susceptibility to, 10 2018-05-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln358Serfs*13) in the POT1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs750470470, ExAC 0.01%). This variant has been reported in a family affected with chronic lymphocytic leukemia (PMID: 27528712). The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in POT1 cause disease. 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.

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.