Together, the absence of a phenotype in TUBB3 knockout mice, the isolated CFEOM phenotype found with variants that have poor heterodimer formation and lower microtubule incorporation, and the more severe phenotypes found with variants that form heterodimers and incorporate into microtubules support an altered- or gain-of-function disease mechanism that is dependent on mutant TUBB3 incorporation into microtubules. This evidence concerns the gene TUBB3 and congenital fibrosis of the extraocular muscles.