Table 1. Private variants shared by the affected cousins of each exome-sequenced family.

Family id	Position	Gene	Nucleotide/ AA change	SIFT	Polyphen-2	GERP
74-0668	chr14:104029378	APOPT1	c.C79A:p.P27T	0.01	0	−1.81
	chr19:35850022	FFAR3	c.A230G:p.N77S	0.88	0.003	−6.53
152MM0304	chr1:3328298	PRDM16	c.G1537A:p.G513S	0.75	0.852	2.22
	chr2:167108286	SCN9A	c.G3428T:p.C1143F	0	1	5.82
156-3860	chr6:167594182	TCP10L2	c.A831T:p.E277D	1	0	−1.58
	chr8:144991583	PLEC	c.G12364C:p.V4122L	0.99	1	5.08
	chr11:32636075	CCDC73	c.G1789C:p.E597Q	0.41	0.047	1.63
	chr19:55998317	NAT14	c.C615G:p.D205E	0.1	0.009	0.636
156-3897	chr19:8399390	KANK3	c.C1321G:p.P441A	0.23	0.131	3.36
	chr19:58117083	ZNF530	c.A190T:p.T64S	0.79	0.001	−3.39
152MM0122	chr2:233712266	GIGYF2	c.G3651C:p.Q1217H	0.06	0.22	−2.51

Abbreviations: AA, amino acid; GERP, genomic evolutionary rate profiling; PolyPhen-2, polymorphism phenotyping v2; SIFT, sorting intolerant from tolerant.

SIFT predicts impact of amino acid substitutions based on the degree of conservation in sequence alignments derived from closely related sequences. Scores <0.05 are considered deleterious. PolyPhen-2 predicts impact of a variant on the structure and function of a human protein using eight sequence-based and three structure-based predictive features. Scores >0.95 are considered probably damaging. GERP identifies functional constraint of a sequence variant by quantifying substitution deficits in multiple alignments. Substitution deficits represent a natural measure of constraint that reflects the strength of past purifying selection. Higher GERP scores are more deleterious.

Genes selected for case–control study are noted in bold.