In this region, missense variants have been associated with severe phenotypes [e.g. ACG2, Kniest dysplasia (MIM #156,550), Spondyloepiphyseal dysplasia (congenital type, SEDC, MIM #183,900)], whereas loss-of-function variants (e.g. nonsense variants, splice site variants, frameshift variants) have been mainly described in patients with milder phenotypes such as Stickler syndrome, type 1 (STL1)4,8,9. The gene discussed is COL2A1; the disease is Stickler syndrome type 1.