ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000003.11) (NC_000003.12)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

Krakow D et al. 2004 PMID: 14991055 Nonsense mutations affecting both alleles of FLNB have been shown to cause autosomal recessive spondylocarpotarsal synostosis syndrome (OMIM 272460). This study also identified autosomal dominant missense mutations or in-frame deletions are associated with a spectrum of skeletal dysplasias which include atelosteogenesis (AO) type I (OMIM 108720), atelosteogenesis type III (OMIM 108721) and Larsen syndrome (OMIM 150250). Bicknell LS et al. 2005 PMID: 15994868 identified heterozygous missense mutations of FLNB in patients with autosomal dominant boomerang dysplasia (OMIM 112310). Per GeneReviews, the "Larsen syndrome ? AO spectrum of conditions...are caused by normal expression of a structurally abnormal FLNB protein. " There is no evidence at this time to suggest that loss of a single copy of FLNB causes an abnormal phenotype. As such, we are giving this gene a score of 0 (in relation to the autosomal dominant phenotypes), and intend to reevaluate if additional evidence becomes available.

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

Triplosensitivity phenotype comment:

At the time of this review, there is no evidence to suggest focal duplications of this gene cause an abnormal phenotype.