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
20711175 Ng et al. described ten patients with Kabuki syndrome and "de novo" LoF mutations in KMT2D gene.
21671394 Hannibal et al. described 25 patients with Kabuki syndrome and "de novo" LoF mutations which were located all over KMT2D gene. The majority of variants found to cause Kabuki syndrome were novel nonsense or frameshift mutations.
21607748 Li et al. described eleven patients with Kabuki syndrome and "de novo" LoF mutations at KMT2D gene: Three nonsense mutations, two splice-site mutations, six small deletions or insertions.

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.