Table 3.

Summary of homology modelling and functional analysis

Gene	Variant	In silico	Conservation	In vitro consequences
TUBA1A	p.Arg214His (c.641G>A)	Alpha-helix 6. Within intradimer and interprotofilament interfaces	αArg214 conserved in most alpha-tubulin isoforms	Incorporates into microtubules but at a reduced rate following cold-induced depolymerization
	p.Ile219Val (c.655A>G)	Loop between alpha-helices 6 and 7	αIle219 conserved throughout alpha-tubulin isoforms	Not determined
TUBB2B	p.Gly13Ala (c.38G>C)	Alpha-helix 1. Within beta-tubulin core. Three predicted H-bonds between β-subunit and GDP disrupted	βGly13 hyperconserved in both beta- and alpha-tubulin isoforms	Reduced incorporation into microtubules
TUBB3	p.Glu288Lys (c.862G>A)	Alpha-helix 9. Within interprotofilament interface. Loss of two H-bonds with Thr285 (intrasubunit) predicted	βGlu288 conserved in beta- and most alpha-tubulin isoforms	Does not incorporate into microtubules
	p.Pro357Leu (c.1070C>T)	Loop between beta-strands 9 and 10. Facing microtubule lumen	βPro357 hyperconserved in both beta- and alpha-tubulin isoforms	Does not incorporate into microtubules