Supplementary table 2A. Proband-specific variants Proband Gene Gene full name Chr Position RefSeqChange Function ESP6500 1000 Genome SNP137 PolyPhen2 Nucleotide Amino acid Score Prediction 1 AGAP5 ArfGAP with GTPase domain, ankyrin repeat and PH domain 5 chr10 75435178 NM_001144000 c.G1240A p.V414M exonic . 0.99 D 1 REXO1L1 REX1, RNA exonuclease 1 homolog (S. cerevisiae)-like 1 chr8 86574465 NM_172239 c.A1262G p.Y421C exonic . 0.98 D 1 COL4A3 collagen, type IV, alpha 3 (Goodpasture antigen) chr2 228169782 NM_000091 c.G4235T p.G1412V exonic . 1.00 D 1 KIAA1586 KIAA1586 chr6 56912133 NM_020931 c.C44G p.A15G exonic . 0.99 D 1 KIAA1586 KIAA1586 chr6 56912176 NM_020931 c.C87G p.D29E exonic . 0.99 D 1 JAKMIP3 Janus kinase and microtubule interacting protein 3 chr10 133955524 NM_001105521 c.G1574C p.G525A exonic . 1.00 D 1 MPHOSPH8 M-phase phosphoprotein 8 chr13 20240685 NM_017520 c.C2140T p.L714F exonic . 0.97 D 1 SYNE1 spectrin repeat containing, nuclear envelope 1 chr6 152783902 NM_033071 c.A2242T p.N748Y exonic . 0.97 D 1 CAND2 cullin-associated and neddylation-dissociated 2 (putative) chr3 12858835 NM_012298 c.C2125T p.H709Y exonic . 0.95 D 1 TDRD9 tudor domain containing 9 chr14 104460909 NM_153046 c.T1289G p.V430G exonic . 0.96 D 2 ASPM asp (abnormal spindle) homolog, microcephaly associated (Drosophila)chr1 197091625 NM_001206846 c.G3491A p.R1164H exonic . 0.99 D 2 ADAM29 ADAM metallopeptidase domain 29 chr4 175896951 NM_001130705 c.A275G p.D92G exonic . 1.00 D 2 BCO2 beta-carotene oxygenase 2 chr11 112087019 NM_001256398 c.G1373A p.G458E exonic . 1.00 D 2 CATSPERD catsper channel auxiliary subunit delta chr19 5748225 NM_152784 c.C863T p.S288F exonic . 0.96 D 2 SCUBE2 signal peptide, CUB domain, EGF-like 2 chr11 9077346 NM_001170690 c.T1201C p.C401R exonic . 1.00 D 2 POLQ polymerase (DNA directed), theta chr3 121207798 NM_199420 c.A3980C p.Q1327P exonic . 1.00 D 2 GCN1L1 GCN1 general control of amino-acid synthesis 1-like 1 (yeast) chr12 120574319 NM_006836 c.T6995C p.L2332P exonic . 0.98 D 2 HARS histidyl-tRNA synthetase chr5 140058663 NM_002109 c.G446A p.R149H exonic . 1.00 D 2 GUF1 GUF1 GTPase homolog (S. cerevisiae) chr4 44691909 NM_021927 c.G1252A p.E418K exonic . 0.94 D 2 HTRA3 HtrA serine peptidase 3 chr4 8288500 NM_053044 c.T698A p.I233N exonic . 0.99 D 2 MR1 major histocompatibility complex, class I-related chr1 181018275 NM_001194999 c.C155T p.S52L exonic . 1.00 D 2 MAN2C1 mannosidase, alpha, class 2C, member 1 chr15 75651046 NM_001256496 c.C1948T p.R650W exonic . 0.98 D 2 MTTP microsomal triglyceride transfer protein chr4 100534247 NM_000253 c.G2167A p.D723N exonic . 0.98 D 2 MUC5B mucin 5B, oligomeric mucus/gel-forming chr11 1266892 NM_002458 c.C8782T p.R2928W exonic . 0.93 D 2 NRXN1 neurexin 1 chr2 50170860 NM_138735 c.C1003G p.P335A exonic . 1.00 D 2 PDCD6 programmed cell death 6 chr5 272863 NM_013232 c.G139C p.E47Q exonic . 1.00 D 2 PARP6 poly (ADP-ribose) polymerase family, member 6 chr15 72552919 NM_020214 c.A656G p.N219S exonic . 0.96 D 2 RIN3 Ras and Rab interactor 3 chr14 93119252 NM_024832 c.G1858C p.V620L exonic . 0.95 D 2 STRC stereocilin chr15 43905037 NM_153700 c.G2735A p.R912H exonic . 0.99 D 2 TPPP3 tubulin polymerization-promoting protein family member 3 chr16 67424855 NM_015964 c.G160A p.D54N exonic . 0.99 D 2 DCAF10 DDB1 and CUL4 associated factor 10 chr9 37860120 NM_024345 c.C1241T p.T414M exonic . 1.00 D 2 ZC3H4 zinc finger CCCH-type containing 4 chr19 47572384 NM_015168 c.C2363T p.A788V exonic . 0.99 D 3 AGAP8 ArfGAP with GTPase domain, ankyrin repeat and PH domain 8 chr10 51246226 NM_001077686 c.C184T p.L62F exonic . 0.99 D 3 CCM2L cerebral cavernous malformation 2-like chr20 30602783 NM_080625 c.G107A p.R36H exonic . 1.00 D 3 DOCK9 dedicator of cytokinesis 9 chr13 99555230 NM_001130049 c.C1175G p.T392R exonic . 1.00 D 3 DNER delta/notch-like EGF repeat containing chr2 230456495 NM_139072 c.G386T p.G129V exonic . 1.00 D 3 DUX2 double homeobox 2 chr10 135494906 splicing . 3 DYTN dystrotelin chr2 207564560 NM_001093730 c.C610T p.P204S exonic . 1.00 D 3 GPAT2 glycerol-3-phosphate acyltransferase 2, mitochondrial chr2 96692778 NM_207328 c.C796T p.L266F exonic . 0.99 D 3 ABCB8 ATP-binding cassette, sub-family B (MDR/TAP), member 8 chr7 150739159 NM_007188 c.A1729C p.I577L exonic . 0.97 D 3 KLHL18 kelch-like family member 18 chr3 47382078 NM_025010 c.G1138A p.V380M exonic . 0.95 D 3 EEF1A1 eukaryotic translation elongation factor 1 alpha 1 chr6 74229160 NM_001402 c.T224C p.I75T exonic . 1.00 D 3 ZNF705D zinc finger protein 705D chr8 11970359 NM_001039615 c.C595T p.P199S exonic . 0.99 D 3 FAM72D family with sequence similarity 72, member D chr1 143897564 NM_207418 c.G433C p.E145Q exonic . 1.00 D 3 MSLNL mesothelin-like chr16 820921 NM_001025190 c.C2464T p.R822W exonic . 0.99 D 3 OBSCN obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF chr1 228433336 NM_001098623 c.A3704C p.E1235A exonic . 1.00 D 3 ODZ1 teneurin transmembrane protein 1 chrX 123554168 NM_014253 c.G4954A p.V1652 exonic . 0.97 D 3 OR2G2 olfactory receptor, family 2, subfamily G, member 2 chr1 247751981 NM_001001915 c.C320G p.S107C exonic . 0.97 D 3 TAF5L TAF5-like RNA polymerase II, p300/CBP-associated factor (PCAF)-associatedchr1 229738666 factor, 65kDa NM_001025247 c.A248T p.D83V exonic . 0.93 D 3 PRAMEF5 PRAME family member 5 chr1 13109097 NM_001013407 c.C1172G p.S391C exonic . 1.00 D 3 PREPL prolyl endopeptidase-like chr2 44569557 NM_001042385 c.A751G p.S251G exonic . 0.96 D 3 DNAH7 dynein, axonemal, heavy chain 7 chr2 196771421 NM_018897 c.G4297C p.G1433R exonic . 1.00 D 3 FAM108A1 abhydrolase domain containing 17A chr19 1877546 NM_001130111 c.C668G p.P223R exonic . 0.92 D 3 ATP2C2 ATPase, Ca++ transporting, type 2C, member 2 chr16 84494285 NM_014861 c.G2359A p.D787N exonic . 1.00 D 3 KRT7 keratin 7 chr12 52627304 NM_005556 c.C224G p.P75R exonic . 1.00 D 3 PCDHB11 protocadherin beta 11 chr5 140580510 NM_018931 c.A1163T p.D388V exonic . 0.95 D 3 SEMA3E sema domain, immunoglobulin domain (Ig), short basic domain, secreted,chr7 82997097 (semaphorin) NM_001178129 3E c.G1953T p.K651N exonic . 1.00 D 3 SIGLEC5 sialic acid binding Ig-like lectin 5 chr19 52133563 NM_003830 c.T26C p.L9P exonic . 0.97 D 3 STAG2 stromal antigen 2 chrX 123185227 NM_006603 c.A1179T p.L393F exonic . 0.99 D 3 ZNF486 zinc finger protein 486 chr19 20308501 NM_052852 c.G982C p.G328R exonic . 0.99 D 4 ANKRD20A1 ankyrin repeat domain 20 family, member A1 chr9 67934721 splicing . 4 ATG9A autophagy related 9A chr2 220089227 NM_024085 c.G866A p.R289H exonic . 0.96 D 4 CAMSAP2 calmodulin regulated spectrin-associated protein family, member chr12 200730102 NM_203459 c.A275G p.D92G exonic . 1.00 D 4 CHCHD5 coiled-coil-helix-coiled-coil-helix domain containing 5 chr2 113343842 NM_032309 c.G209A p.R70Q exonic . 0.91 D 4 CSGALNACT1 chondroitin sulfate N-acetylgalactosaminyltransferase 1 chr8 19362817 NM_001130518 c.C529T p.R177W exonic . 1.00 D 4 PPIP5K1 diphosphoinositol pentakisphosphate kinase 1 chr15 43857181 NM_001130859 c.G3056T p.C1019F exonic . 0.96 D 4 PPIP5K1 diphosphoinositol pentakisphosphate kinase 1 chr15 43870347 NM_001130859 c.C1171A p.L391I exonic . 1.00 D 4 EP400 E1A binding protein p400 chr12 132529360 NM_015409 c.A6646C p.T2216P exonic . 0.98 D 4 FAM21A family with sequence similarity 21, member A chr10 51840665 NM_018232 c.C238T p.R80W exonic . 1.00 D 4 FAM21A family with sequence similarity 21, member A chr10 51885192 NM_018232 c.G2407T p.A803S exonic . 1.00 D 4 GLB1L2 galactosidase, beta 1-like 2 chr11 134241716 NM_138342 c.A1499G p.Q500R exonic . 0.92 D 4 TTN titin chr2 179434826 NM_003319 c.G48838A p.D16280N exonic . 1.00 D 4 MUC4 mucin 4, cell surface associated chr3 195513694 NM_018406 c.C4757T p.P1586L exonic . 0.96 D 4 MUC4 mucin 4, cell surface associated chr3 195514022 NM_018406 c.G4429C p.D1477H exonic . 0.92 D 4 FAM168B family with sequence similarity 168, member B chr2 131810487 NM_001009993 c.C577T p.P193S exonic . 0.99 D 4 FAM21C family with sequence similarity 21, member C chr10 46235668 NM_001169106 c.C502T p.R168W exonic . 1.00 D 4 FAM115C family with sequence similarity 115, member C chr7 143400211 NM_001130025 c.G124A p.V42M exonic . 0.99 D 4 FAM21B family with sequence similarity 21, member B chr10 47896803 NM_018232 c.C238T p.R80W exonic . 1.00 D 4 FAM21B family with sequence similarity 21, member B chr10 47941337 NM_018232 c.G2407T p.A803S exonic . 0.96 D 4 SPATA31A5 SPATA31 subfamily A, member 5 chr9 65507184 NM_001113541 c.G376A p.V126M exonic . 0.97 D 4 KRT76 keratin 76 chr12 53170913 NM_015848 c.A163C p.S55R exonic . 0.94 D 4 KRTAP5-11 keratin associated protein 5-11 chr11 71293819 NM_001005405 c.G65T p.G22V exonic . 0.99 D 4 LARP1 La ribonucleoprotein domain family, member 1 chr5 154179154 NM_015315 c.C1150A p.L384I exonic . 1.00 D 4 LRRC16B leucine rich repeat containing 16B chr14 24535653 NM_138360 c.G3572A p.R1191Q exonic . 0.99 D 4 KDM4E lysine (K)-specific demethylase 4E chr11 94759407 NM_001161630 c.C686T p.P229L exonic . 1.00 D 4 LOXL3 lysyl oxidase-like 3 chr2 74776687 NM_032603 c.G501C p.E167D exonic . 0.97 D 4 CLEC18C C-type lectin domain family 18, member C chr16 70217697 NM_173619 c.G919A p.D307N exonic .