ClinGen Dosage Sensitivity Curation Page

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  • Curation Status: Complete

Location Information

Select assembly: (NC_000009.11) (NC_000009.12)
Evidence for haploinsufficiency phenotype
PubMed ID Description
21358634 Goudie et al. (2011): 11 mutations identified amongst 18 different families (22 families total tested) with multiple self-healing squamous epitheliomas, including >3 nonsense and frameshift mutations predicting to result in protein truncation.

Haploinsufficiency phenotype comments:

The haploinsufficiency rating here is based on the multiple self-healing squamous epithelioma phenotype. TGFBR1 mutations are also associated with Loeys-Dietz syndrome; the mutational mechanisms associated with this syndrome are incompletely understood, though evidence is emerging to suggest that mutations associated with this phenotype are gain-of-function mutations. See the Loeys-Dietz GeneReview (under "Abnormal Gene Product" in the "Molecular Genetics" section for a full discussion) (

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

Breckpot et al. (2010): A report of a 17-year-old boy with pubertas tarda, a bifid uvula, camptodactyly and facial dysmorphic features, which the authors describe as suggestive of Loeys Dietz syndrome. No evidence of any arterial tortuosity or other cardiac abnormality was seen on echocardiography or abdominal ultrasound at 17 years of age. Mutation analysis of TGFBR1 and TGFBR2 was normal, but the individual was found to have a 120 kb deletion on chromosome 22q13.31q13.32, inherited from an unaffected parent, and a de novo 14.6 Mb duplication on chromosome 9q22.32q31.3, comprising TGFBR1 (along with 56 other genes) (PMID:20813212). Though it is possible that the duplication of TGFBR1 could be contributing to the patient's features, this cannot be definitively stated.