ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000015.9) (NC_000015.10)
Evidence for haploinsufficiency phenotype
PubMed ID Description
14657428 Abuzzahab et al. (2003) analyzed 51 patients with short stature and found a R59X mutation in IGF1R in one patient. His mother and half sib also had the mutation and were both small for gestational age at birth. The mother was reported to be short.
19240156 Fang et al. (2009) studied a family (proband, mother, sib) with short stature for mutations in IGF1R and found a 19 bp duplication in exon 18 which results in a premature stop codon.
21811077 Mohn et al. (2011) reported a family (proband, sib, 2 pat aunts) with short stature and a nonsense mutation in IGF1R (Tyr387X).

Haploinsufficiency phenotype comments:

Patients with heterozygous deletion involving IGF1R showed consistent growth restriction phenotype. LOF mutations that caused nonsense-mediated decay also result in the same consequence. Other references of interest include PMIDs: 24296753, 20962017, and 14671200.

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

Triplosensitivity phenotype comment:

As no focal duplications of IGF1R have been reported, the triplosensitivity score of this gene is 0. However, evidence from multiple independent cases support the association of increased IGF1R copy number with overgrowth syndrome due to 15q terminal duplication. The definitive evidence is currently lacking to support that IGF1R alone is sufficient to cause overgrowth phenotype. Relevant literature is summarized below: PMID 26689622: Leffler et al (2016) reported two familial microduplications of 15q26.3 causing overgrowth and variable intellectual disability with normal copy number of IGF1R, suggesting the possibility that the distal region of 15q contains another gene regulating human growth. PMID 19133692: Tatton-Brown et al. (2009) describe a case of 15q overgrowth syndrome caused by duplications of distal 15q, which include IGF1R. Additional references of interest include PMIDs: 14671200, 15164417, 12404101, and 22030053.