ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000001.10) (NC_000001.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
21398687 Gardie et al. (2011) identified 32 different heterozygous germline mutations (15 missense, 6 frameshifts, 4 nonsense, 1 deletion/insertion, 5 splicing site and 1 complete deletion). 40 of the 56 families with proven Hereditary Leiomyomatosis and Renal Cell Cancer. Lymphoblstoid cell lines were generated by Epstein-Barr virus transformation of leucocytes. FH enzyme activity was measured spectrophotometrically. A reduction of at least 50% of the enzymatic activity was observed for all mutations tested. A difference of enzyme activities between missense mutations and loss of function mutations (deletions, nonsense mutations, splice site mutations) was NOT observed.

Haploinsufficiency phenotype comments:

Heterozygous loss of function variants result in autosomal dominant Leiomyomatosis and renal cell cancer. Biallelic variants result in autosomal recessive fumarase deficiency

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity
Evidence for triplosensitivity phenotype
PubMed ID Description

Triplosensitivity phenotype comment:

no evidence for triplosensitivity