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
25217958 Coe et al. (2014) reviewed nine patients with presumably loss of function, several known to be de novo, mutations and deletions in patients with variable phenotype that can include expressive language delays and intellectual disabilities.
25356899 Hamdan et al. (2014) reports de novo truncating mutations in a patient with moderate non-syndromic intellectual disability. The additional clinical information from the supplemental materials indicates this is a 6.5 year old with only 2-3 word sentences, supporting the presence of expressive language delays.

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.