ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function 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.

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.