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
7990924 Foster et al. (1994) found a de novo nonsense change (195X) in SOX9 in a 46,XX female with CD and a de novo 4-bp insertion resulting in a frameshift in a 46,XY female in an aborted fetus with short limbs, cystic hygroma, micrognathia and normal female genitalia.
8894698 Cameron et al. (1996) identified a family with 3 affected individuals with CD and sex reversal. They found a 1-bp insertion in SOX9, resulting in a frameshift and stop codon. The 3 individuals carried the same mutation, but varied with respect to the gonadal phenotype. The father was shown to be a germ-line mosaic for the mutation.
8001137 Wagner et al. (1994) found a de novo nonsense mutation in SOX9 (Y44OX) in an XY female with CD.

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.