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
14585638 Yagi et al (2003) identified a heterozygous 1 base pair deletion (1223delC) in the TBX1 gene in a mother, son, and daughter with conotruncal anomaly face syndrome/velocardiofacial syndrome. The deletion caused a frameshift leading to a stop codon.
16684884 Paylor et al (2006) identified a heterozygous 23 base pair deletion (1320-1342del23) in the TBX1 gene in a mother and 2 sons with velocardiofacial syndrome. The deletion caused a frameshift and extension of the protein from 504 to 616 amino acids. Additional phenotypes in the family included major depression in the mother and Asperger syndrome in one of the sons. Using expression of a CAT-reporter protein as a read-out for transcriptional activity, they show that wild-type TBX1 activated the CAT reporter whereas the mutant constructs 1223delC (called 1250delC in this paper) and 1320-1342del23bp did not.

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.