ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000003.11) (NC_000003.12)
Evidence for haploinsufficiency phenotype
PubMed ID Description
27915094 In the DDD study, Kharbanda et al. identified 10 probands with de novo loss of function (truncating) sequence variants in CTNNB1. The common phenotype included intellectual disability, postnatal microcephaly, truncal hypotonia and peripheral spasticity, mild dysmorphic features and behavioural problems. An additional proband was identified in the DECIPHER database with overlapping phenotypic features but clinical information was incomplete.
23033978 In 3 patients with severe intellectual disability, microcephaly, and spasticity, de Ligt et al identified heterozygous loss-of-function mutations in the CTNNB1 gene. Two were de novo and the third could not be resolved for inheritance (dad was unavailable).
25326669 16 individuals from 15 families were found to have newly identified loss-of-function CTNNB1 mutations. Virtually all were de novo events. Phenotype included intellectual disability, motor delay, speech impairment, and abnormal muscle tone (truncal hypotonia and distal hypertonia/spasticity).

Haploinsufficiency phenotype comments:

Additional PMIDs: 28575650; 28514307; 24668549; 26968164

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