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
12668170 Wollnik et al. (2002) reported a frameshift pathogenic variant (TBX3: c.88_89insA , M30fsX110) segregation among 10 family members spanning 3 generations in a large Turkish family affected with ulnar-mammary syndrome. The phenotypic expression of the disease was highly variable among the affected family members.
28145909 Tanteles et al. (2017) identified a heterozygous pathogenic variant (TBX3: c.1423C>T, p.Glu475Ter) in a Cypriot family in which twin brothers and their father had ulnar-mammary syndrome. The variant segregated with the disorder in the family. The twins showed classic features of the disorder, whereas their father was mildly affected.
12116211 Sasaki et al. (2002) identified a heterozygous pathogenic variant (TBX3: TBX3: c.817A>T, p.Lys273Ter) in a Japanese mother and her 2 sons with ulnar-mammary syndrome, micropenis with or without cryptorchidism, and hypoplastic nipples in the brothers; and hypoplastic mammary glands and nipples, poor perspiration, and bicornuate uterus in the mother.

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.