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
23253743 Petersen, et al. (2012) report a 3 1/2 year old male who presented with autism features, intellectual disabilities, strabismus, and cranial nerve VI palsy. He had a prominent nasal bridge and behavior problems. The patient was found to carry a 473 kb deletion that removed the first four exons of CHRM3. No functional/expression studies were performed to determine whether the mutant CHRM3 allele retained any residual activity and parental studies were not available.

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.