Table 1. Variants of potential significance identified in family.

Gene	Chr	Start chr posn (hg19)	End chr posn (hg19)	Ref	Variant	transcript:exon:AAChange	freq1	PhyloP3	SIFT4	PolyPhen2 HDIV5
Validated
RIC3	chr11	8161603	8161603	C	T	NM_001206671,NM_001206672, NM_024557:exon2:c.G262A:p.G88R	novel	2.625	0.03	0.999
RIPK1	chr6	3105973	3105973	C	G	NM_003804: exon8:c.C1264G:p.Q422E	novel	2.641	0.18	0.082
ZBED5	chr11	10874596	10874596	G	A	NM_001143667,NM_021211: exon3:c.C1897T:p.R633C	novel	2.274	0.01	1.000
HERC2	chr15	28491062	28491062	T	A	NM_004667: exon23:c.A3542T:p.D1181V	novel2	1.168	0.38	0.999
Not Validated
TMF1	chr3	69096995	69097006	GTGAAGACTTGA	TTGGAGTCTTGC	NM_007114: exon2:c.850_861	novel
TMF1	chr3	69097012	69097012	A	ACCTTAGGCTTT	NM_007114: exon2:c.844_844delins ACCTTAGGCTTT	novel
MFSD1	chr3	158519825	158519825	C	CTGTCAAGACGGCG	NM_001167903,NM_022736: exon1:c.31_31delinsCTGTCAAGACGGCG	novel
PPP3CB	chr10	75227315	75227315	T	A	NM_001142353,NM_001142354,NM_021132: exon9:c.A1104T:p.E368D	novel
C15orf40	chr15	83677185	83677185	A	ACAAAATCTT	NM_001160113: exon3:c.481_481delinsAAGATTTTGT	novel

1–control frequency across 1000Genomes (all samples) and exome variant server (all samples).

2–validated only in the proband.

Three functional predictions are shown here (PhyloP, SIFT and PolyPhen2). A larger set of predictions is presented in Supplementary table S14.

3–PhyloP considers conservation of given base at the DNA level across species. A positive score represents a conserved base.

4–SIFT considers the conservation of bases and motifs at the protein level. SIFT scores ≤0.05 are considered deleterious. 5 – Polyphen2 considers the physical properties of amino acids. The HumDiv algorithm (shown here) is most suitable for fully penetrant Mendelian mutations. Polyphen scores ≥0.95 are considered damaging.