ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000001.10) (NC_000001.11)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

Osbun et al. (PMID: 21739582): This paper reports 4 potential pathogenic variants in DISC1 individuals with agenesis of the corpus callosum. Two of these were found in normal populations. One splice site mutation was also reported which disrupted the splice acceptor site; real time PCR showed reduced mRNA levels of the exon with the mutation in the patient. All mutations were inherited but parental phenotypic information was not available. Sachs et al (PMID: 15940305) also report a frameshift mutation at the 3' end of DISC1 in multiple individuals with schizophrenia and schizoaffective disorder in one family. Other indivudals in the family with various other mental illness diagnoses were negative. However, Green at al. (PMID: 16936759) report a case-control study where this mutation was not found in 655 patients with schizophrenia and was detected in 2 of 694 matched controls. Millar et al. (PMID: 10814723) report characterization of a balanced translocation that interrupts DISC1 in a family with extensive and variable psychiatric disease.

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

Triplosensitivity phenotype comment:

Also, a large duplication including several genes has been reported in association with autism but was inherited from the normal mother (PMID 20002455).