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
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).

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.