ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.956_959del (p.Thr319fs) (rs398123330)

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
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000078630 SCV000110486 pathogenic not provided 2013-03-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV000491886 SCV000580026 pathogenic Hereditary cancer-predisposing syndrome 2020-09-26 criteria provided, single submitter clinical testing ​The c.956_959delCTTT pathogenic mutation, located in coding exon 8 of the PTEN gene, results from a deletion of 4 nucleotides at positions 956 to 959, causing a translational frameshift with a predicted alternate stop codon (p.T319Kfs*24). This mutation has been reported in a patient meeting relaxed International Cowden Consortium operational criteria for Cowden Syndrome at age 40 (Tan et al. Am J Hum Genet. 2011 Jan 7;88(1):42-56). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.
Invitae RCV000801647 SCV000941434 pathogenic PTEN hamartoma tumor syndrome 2019-11-18 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the PTEN gene (p.Thr319Lysfs*24). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 85 amino acids of the PTEN protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Cowden or Cowden-like syndrome (PMID: 21194675). ClinVar contains an entry for this variant (Variation ID: 92836). This variant disrupts the C-terminus of the PTEN protein. Other variant(s) that disrupt this region (p.Ala333Serfs*10) have been determined to be pathogenic (PMID: 10468583, 10698513, 24905788, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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.