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
10587584 Holder et al (2000) report a girl with early-onset obesity and a balanced translocation between 1p22.1 and 6q16.2. They PCR amplified and sequenced both junctions and found that the translocation deleted only a single base pair of chromosome 6 and none of chromosome 1. On chromosome 6, the translocation breakpoint falls within the first intron of SIM1 and separates the 5' flanking sequence and the first exon from downstream exons. No transcripts on chromosome 1 appear to be disrupted.

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.