ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000010.10) (NC_000010.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
21194675 Tan et al. report a study of 3042 individuals who met relaxed criteria for Cowden Syndrome and report 290 (9.5%) with pathogenic mutations in PTEN. The majority were presumed loss of function mutations - 92 (32%) nonsense mutations, 42 (14%) small deletions, 24 (8%) small insertions, 3 (1%) indels, 8 (3%) large deletions, 19 (7%) splice-site donor mutations, 9 (3%) splice-site acceptor mutations.
32003824 Yehia et al. report on 481 patients with pathogenic germline PTEN variants. This cohort includes those reported in Tan et al (PMID 21194675). The mutation spectrum includes 242 truncating mutations, as well as 12 exon-level deletions.

Haploinsufficiency phenotype comments:

Loss of function mutations in PTEN are associated with macrocephaly and autism as well as hamartomatous tumor syndromes such as Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Proteus-like syndrome. The various PTEN-associated clinical presentations are collectively referred to as PTEN hamartoma tumor syndrome (PHTS).

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

Duplications involving the PTEN gene have been reported in patients with microcephaly and other neurodevelopmental phenotypes (PMID 30301738, 26088875), however these duplications involved additional genes. To our knowledge, no single gene duplications of the entire PTEN locus have been reported.