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
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).

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.