TABLE 1.

Detailed description of the THOC2 variants with supporting molecular evidence.

	Individual	From	Method of identification	Position hg19	NM_001081550	Mode of inheritance	CADD	Provean score	Provean prediction	GERP++	Phylop	gnomAD frequency	Polyphen2*	Variant plasmid tested	Reduced Protein Stability	ACMG pathogenicity classification**
Missense		Kumar et al 2015 AJHG	X-Chr Exome sequencing	122799566	c.1313T>C: p.Leu438Pro	Maternal inheritance	28.1	−6.08	Deleterious	5.7	1.902	absent	D	YES	YES	LP
	1	Australia	Trio WES	122767853	c.2087C>T: p.Thr696Ile	De novo	27.4	−5.47	Deleterious	5.03	0.963	absent	D	YES	YES	DP
	2	USA	WES	122766890	c.2138G>A: p.Gly713Asp	De novo	31	−4.69	Deleterious	5.73	2.412	absent	D	YES	YES	DP
		Kumar et al 2015 AJHG	X-Chr Exome sequencing	122765621	c.2399T>C: p.Ile800Thr	Maternal inheritance	23.9	−4.01	Deleterious	5.97	2.016	absent	P	YES	YES	LP
	3-4	Canada/Germany/Russia Identical twins	WES	122757079	c.3559C>T: p.His1187Tyr	Maternal inheritance; Mother skewed (99.9:0.1%)	23.1	−5.07	Deleterious	6.07	2.571	absent	P	YES	YES	LP
Splice	5	Japan	Trio WES	122757634	Exon28:c.3503+4A>C	Maternal inheritance; Mother skewed 98:2%	10.8	N/A	N/A	5.57	1.86	absent	N/A	N/A	ND	LP
	6	Canada	WES	122747561	Exon35:c.4450-2A>G	Maternal inheritance; Mother skewed 94:6%	23.7	N/A	N/A	5.25	1.735	absent	N/A	Fibroblasts of the affected male proband and carrier mother	NO	LP
Missense	7	USA Epi4K Consortium & Epilepsy Phenome/Genome Project; Nature 501:217-221, 2013	WES	122778639	c.1550A>G: p.Tyr517Cys	De novo	26.6	−7.87	Deleterious	5.84	1.955	absent	D	YES	YES	DP

^*Probably damaging, D; Possibly damaging, P; N/A, not applicable; ND, not determined;

^**De novo Pathogenic, DP; Likely Pathogenic, LP