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
9585603 Krantz et al. (1998) tested 54 Alagille syndrome (AGS) patients and their families for for the frequency of variants in JAG1. They found mutations/deletions in 75% of the patients, including 3 whole-gene deletions, 19 small deletions and insertions, and 9 nonsense mutations. Some of the identified variants were de novo and some were inherited from parents with clinical features consistent with JAG1 or an AGS microform (meaning they had some physical features consisted with AGS but not enough to establish clinical diagnosis).
12497640 Ropke et al. (2003) tested a series of probands with Alagille syndrome for mutations in JAG1. They identified 36 new variants in JAG1, including 23 truncating variants (these included deletions, insertions, complex and nonsense variants). Some of the identified variants were de novo and some were determined to be inherited.
16575836 Warthen et al. (2006) tested 247 probands with diagnosis of Alagille syndrome and found JAG1 mutations in 94% of patients, including over 40 different truncating variants.

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.