Supplementary table 1A. Variants detected in breast cancer-affected members of family 1 Gene DESCRIPTION KEGG Pathway ID KEGG Pathway Description Chr Position RefSeq ExonChange Func ESP6500 1000 Genome dbSNP137 PolyPhen2 Distribution Frequency Nucleotide Amino acid Score Prediction 1 2 3 4 6 7 8 GPRIN1 G protein regulated inducer of neurite outgrowth 1 chr5 176026123 NM_052899 exon2 c.T713C p.L238S exonic 0.91 D -+++++- 5 ZNF335 zinc finger protein 335 chr20 44598182 NM_022095 exon3 c.T350C p.M117T exonic 1.00 D -+++--+ 4 LRRC66 leucine rich repeat containing 66 chr4 52861746 NM_001024611 exon4 c.A1442T p.D481V exonic 0.96 D --+++-+ 4 NBPF16 neuroblastoma breakpoint family, member 16 chr1 148756665 NM_001102663 exon16 c.G1994T p.G665V exonic 0.92 D ++-++-- 4 GPR116 G protein-coupled receptor 116 chr6 46826012 NM_001098518 exon17 c.G3628C p.E1210Q exonic 1.00 D -+++--- 3 ANKRD20A1 ankyrin repeat domain 20 family, member A1 chr9 67934829 NM_001012419 exon4 c.G599A p.R200Q splicing 1.00 D --++--+ 3 RBMXL1 RNA binding motif protein, X-linked-like 1 chr1 89449011 NM_019610 exon2 c.C499G p.P167A exonic 1.00 D +---++- 3 COL12A1 collagen, type XII, alpha 1 chr6 75864212 NM_004370 exon17 c.A3485C p.D1162A exonic 0.85 D --+--++ 3 ANKRD20A1 ankyrin repeat domain 20 family, member A1 chr9 67935957 NM_001012419 exon5 c.C682A p.Q228K exonic 0.81 P -+-++-- 3 ITGB1BP1 integrin beta 1 binding protein 1 chr2 9546989 NM_022334 exon6 c.T427A p.S143T exonic 0.75 P -+++--- 3 AVIL advillin chr12 58197038 NM_006576 exon15 c.T1954C p.W652R exonic 1.00 D ----++- 2 MYH3 myosin, heavy chain 3, skeletal muscle, embryonic hsa05416 Viral myocarditis chr17 10533244 NM_002470 exon39 c.A5573G p.D1858G exonic 1.00 D -+-+--- 2 RNF215 ring finger protein 215 chr22 30775768 NM_001017981 exon8 c.A1043G p.H348R exonic 1.00 D --++--- 2 ANKRD44 ankyrin repeat domain 44 chr2 197986226 NM_001195144 exon8 c.G736A p.A246T exonic 0.99 D ----++- 2 ITPR2 inositol 1,4,5-trisphosphate receptor, type 2 hsa05010 Alzheimer's disease chr12 26839489 NM_002223 exon11 c.C1073T p.P358L exonic 0.99 D ----+-+ 2 USP28 ubiquitin specific peptidase 28 chr11 113683049 NM_020886 exon16 c.A1921G p.S641G exonic 0.99 D --++--- 2 ZNF417 zinc finger protein 417 chr19 58421230 NM_152475 exon3 c.A416G p.Q139R exonic 0.99 D -++---- 2 ZNF587 zinc finger protein 587 chr19 58370196 NM_001204817 exon3 c.A413G p.Q138R exonic 0.99 D -++---- 2 TIGD2 tigger transposable element derived 2 chr4 90034310 NM_145715 exon1 c.C185T p.T62I exonic 0.99 D ----+-+ 2 NUP35 nucleoporin 35kDa chr2 184016246 NM_138285 exon5 c.G408C p.M136I exonic 0.98 D ----++- 2 FLG filaggrin chr1 152276761 NM_002016 exon3 c.A10601G p.N3534S exonic 0.98 D +---+-- 2 GOLGA8A golgin A8 family, member A chr15 34677275 NM_181077 exon7 c.G541A p.A181T exonic 0.96 D --+---+ 2 TEX15 testis expressed 15 chr8 30702074 NM_031271 exon1 c.C4460T p.T1487I exonic 0.88 D ----++- 2 ANKRD20A2 ankyrin repeat domain 20 family, member A2 chr9 42377496 NM_001012419 exon5 c.C682A p.Q228K exonic 0.81 P -+----+ 2 ACADVL acyl-CoA dehydrogenase, very long chain hsa01100 Metabolic pathways chr17 7125576 NM_001033859 exon8 c.A767T p.K256M exonic 0.81 P -+-+--- 2 GOLGA8A golgin A8 family, member A chr15 34674259 NM_181077 exon14 c.C1363T p.R455C exonic 0.70 P ---+--+ 2 C11orf82 chromosome 11 open reading frame 82 chr11 82643815 NM_145018 exon6 c.T1435A p.L479I exonic 0.63 P --++--- 2 ARID4B AT rich interactive domain 4B (RBP1-like) chr1 235346016 NM_031371 exon19 c.C1960T p.H654Y exonic 0.47 P -++---- 2 ANKRD20A1 ankyrin repeat domain 20 family, member A1 chr9 67938656 NM_001012419 exon6 c.C791G p.S264X stopgain 0.57 --+++-- 3 ABCC6 ATP-binding cassette, sub-family C (CFTR/MRP), memberhsa02010 6 ABC transporters chr16 16269844 NM_001171 exon21 c.2591-1G>T splicing - - + + - - - 2 ALDOA aldolase A, fructose-bisphosphate hsa01100 Metabolic pathways chr16 30066250 splicing - - - - + - + 2 PINK1 PTEN induced putative kinase 1 hsa05012 Parkinson's disease chr1 20972051 NM_032409 exon5 c.960-2A>G splicing - - + + - - - 2 ANAPC1 anaphase promoting complex subunit 1 hsa04914 Progesterone-mediated oocyte maturation chr2 112573216 NM_022662 exon28 c.C3328T p.R1110C exonic 1.00 D -----+- 1 CTBP2 C-terminal binding protein 2 hsa05220 Chronic myeloid leukemia chr10 126683225 NM_022802 exon5 c.G2213C p.R738P exonic 1.00 D ---+--- 1 ECI2 enoyl-CoA delta isomerase 2 hsa04146 Peroxisome chr6 4130638 NM_001166010 exon4 c.C379T p.R127W exonic 1.00 D ---+--- 1 GTF2I general transcription factor IIi hsa03022 Basal transcription factors chr7 74163734 NM_001518 exon24 c.C2243T p.P748L exonic 1.00 D --+---- 1 IGSF10 immunoglobulin superfamily, member 10 chr3 151156303 NM_001178145 exon2 c.T127G p.C43G exonic 1.00 D -+----- 1 KRT80 keratin 80 chr12 52579353 NM_001081492 exon2 c.C319T p.R107C exonic 1.00 D ---+--- 1 MAS1L MAS1 oncogene-like chr6 29454897 NM_052967 exon1 c.G783T p.R261S exonic 1.00 D ---+--- 1 PABPC3 poly(A) binding protein, cytoplasmic 3 chr13 25670625 NM_030979 exon1 c.G289C p.G97R exonic 1.00 D -----+- 1 TTLL7 tubulin tyrosine ligase-like family, member 7 chr1 84386943 NM_024686 exon11 c.G1277A p.R426Q exonic 1.00 D +------1 ZFAND4 zinc finger, AN1-type domain 4 chr10 46147441 NM_001128324 exon4 c.C301T p.R101C exonic 1.00 D -----+- 1 DHX35 DEAH (Asp-Glu-Ala-His) box polypeptide 35 chr20 37647477 NM_001190809 exon14 c.C1340T p.P447L exonic 1.00 D +------1 ERBB2IP erbb2 interacting protein hsa04621 NOD-like receptor signaling pathway chr5 65370916 NM_001253698 exon22 c.A3698G p.H1233R exonic 1.00 D -+----- 1 FRYL FRY-like chr4 48559492 NM_015030 exon34 c.A4103G p.N1368S exonic 1.00 D ---+--- 1 KRBA2 KRAB-A domain containing 2 chr17 8273461 NM_213597 exon2 c.G470A p.R157H exonic 1.00 D ---+--- 1 PABPC3 poly(A) binding protein, cytoplasmic 3 chr13 25671456 NM_030979 exon1 c.C1120T p.R374C exonic 1.00 D ------+ 1 PROSER1 proline and serine rich 1 chr13 39600439 NM_170719 exon5 c.C389T p.P130L exonic 1.00 D +------1 TES testis derived transcript (3 LIM domains) chr7 115892471 NM_015641 exon6 c.T1018C p.Y340H exonic 1.00 D ----+-- 1 WDR52 WD repeat domain 52 chr3 113115390 NM_001164496 exon14 c.G1754A p.R585H exonic 1.00 D ----+-- 1 CTBP2 C-terminal binding protein 2 hsa05220 Chronic myeloid leukemia chr10 126683235 NM_022802 exon5 c.G2203T p.V735F exonic 1.00 D ---+--- 1 FRG1 FSHD region gene 1 chr4 190883081 NM_004477 exon8 c.T734G p.L245R exonic 1.00 D ----+-- 1 OR4M1 olfactory receptor, family 4, subfamily M, member 1 hsa04740 Olfactory transduction chr14 20249380 NM_001005500 exon1 c.T899G p.M300R exonic 1.00 D ---+--- 1 LGALS9 lectin, galactoside-binding, soluble, 9 chr17 25965331 NM_002308 exon2 c.G82A p.G28R exonic 1.00 D --+---- 1 PIWIL4 piwi-like RNA-mediated gene silencing 4 hsa04320 Dorso-ventral axis formation chr11 94310519 NM_152431 exon4 c.A374G p.Q125R exonic 1.00 D +------1 SPESP1 sperm equatorial segment protein 1 chr15 69238630 NM_145658 exon2 c.G757T p.D253Y exonic 1.00 D +------1 TBC1D15 TBC1 domain family, member 15 chr12 72311484 NM_001146213 exon13 c.A1408C p.N470H exonic 1.00 D ---+--- 1 ITPR3 inositol 1,4,5-trisphosphate receptor, type 3 hsa05010 Alzheimer's disease chr6 33659653 NM_002224 exon54 c.G7406T p.G2469V exonic 1.00 D +------1 FRG1 FSHD region gene 1 chr4 190883080 NM_004477 exon8 c.C733A p.L245M exonic 0.99 D ----+-- 1 PCDH18 protocadherin 18 chr4 138452524 NM_019035 exon1 c.A719G p.N240S exonic 0.99 D -+----- 1 SLC30A7 solute carrier family 30 (zinc transporter), member 7 chr1 101387306 NM_001144884 exon8 c.G751C p.V251L exonic 0.99 D -+----- 1 UNC5A unc-5 homolog A (C. elegans) hsa04360 Axon guidance chr5 176306444 NM_133369 exon14 c.G2318A p.R773Q exonic 0.99 D +------1 EIF4G2 eukaryotic translation initiation factor 4 gamma, 2 hsa05416 Viral myocarditis chr11 10823596 NM_001042559 exon13 c.G1299T p.Q433H splicing 0.99 D +------1 MMRN1 multimerin 1 chr4 90857440 NM_007351 exon6 c.C2609T p.T870I exonic 0.99 D ----+-- 1 PEAK1 pseudopodium-enriched atypical kinase 1 chr15 77472182 NM_024776 exon5 c.A2087C p.E696A exonic 0.99 D -+----- 1 RGPD5 RANBP2-like and GRIP domain containing 5 chr2 111325017 NM_005054 exon4 c.C341A p.A114E exonic 0.99 D ---+--- 1 SGPL1 sphingosine-1-phosphate lyase 1 hsa01100 Metabolic pathways chr10 72628128 NM_003901 exon8 c.A642G p.I214M exonic 0.99 D -----+- 1 GPRIN1 G protein regulated inducer of neurite outgrowth 1 chr5 176026136 NM_052899 exon2 c.G700T p.D234Y exonic 0.99 D ----+-- 1 CTTN cortactin hsa05131 Shigellosis chr11 70279803 NM_001184740 exon16 c.G1384A p.A462T exonic 0.99 D ---+--- 1 CYYR1 cysteine/tyrosine-rich 1 chr21 27938648 NM_052954 exon2 c.A113T p.Y38F exonic 0.99 D +------1 ARSD arylsulfatase D chrX 2833638 NM_001669 exon6 c.G959A p.G320D exonic 0.99 D ---+--- 1 KIF21A kinesin family member 21A chr12 39727028 NM_001173463 exon17 c.C2434T p.R812C exonic 0.98 D +------1 GZF1 GDNF-inducible zinc finger protein 1 chr20 23350809 NM_022482 exon5 c.G1867A p.E623K exonic 0.98 D ---+--- 1 ANKRD20A2 ankyrin repeat domain 20 family, member A2 chr9 42396440 NM_001012419 exon11 c.A1054G p.R352G exonic 0.98 D +------1 ANKRD20A2 ankyrin repeat domain 20 family, member A2 chr9 43105400 NM_001012419 exon11 c.A1054G p.R352G exonic 0.98 D +------1 ATP6AP2 ATPase, H+ transporting, lysosomal accessory protein 2 chrX 40448358 NM_005765 exon2 c.C158T p.S53F exonic 0.97 D +------1 CCDC86 coiled-coil domain containing 86 chr11 60610178 NM_024098 exon1 c.A581T p.E194V exonic 0.97 D ---+--- 1 FCGBP Fc fragment of IgG binding protein chr19 40368666 NM_003890 exon28 c.C12682G p.Q4228E exonic 0.97 D -+----- 1 MAGI2 membrane associated guanylate kinase, WW and PDZhsa04530 domain containing 2 Tight junction chr7 77755014 NM_012301 exon20 c.G3564A p.M1188I exonic 0.97 D +------1 FLG filaggrin chr1 152277128 NM_002016 exon3 c.G10234A p.G3412R exonic 0.97 D +------1 SHROOM1 shroom family member 1 chr5 132160034 NM_133456 exon4 c.C1319G p.P440R exonic 0.97 D +------1 MAT1A methionine adenosyltransferase I, alpha hsa01100 Metabolic pathways chr10 82034820 NM_000429 exon7 c.G904A p.A302T exonic 0.96 D ---+--- 1 MRGPRX3 MAS-related GPR, member X3 chr11 18159696 NM_054031 exon3 c.C947T p.S316L exonic 0.96 D -+----- 1 MUC17 mucin 17, cell surface associated chr7 100684145 NM_001040105 exon3 c.G9448A p.E3150K exonic 0.96 D -+----- 1 ERMN ermin, ERM-like protein chr2 158182113 NM_020711 exon1 c.T42G p.N14K exonic 0.96 D -+----- 1 GGT1 gamma-glutamyltransferase 1 hsa01100 Metabolic pathways chr22 25016941 NM_001032364 exon9 c.C637G p.L213V exonic 0.96 D +------1 GRIK3 glutamate receptor, ionotropic, kainate 3 hsa04080 Neuroactive ligand-receptor interaction chr1 37319270 NM_000831 exon8 c.G1158T p.L386F exonic 0.95 D ----+-- 1 SEC31B SEC31 homolog B (S. cerevisiae) chr10 102267721 NM_015490 exon6 c.G583T p.V195L exonic 0.95 D +------1 ANKRD20A1 ankyrin repeat domain 20 family, member A1 chr9 67934733 NM_001012419 exon4 c.C503T p.T168I exonic 0.95 D --+---- 1 RIMS2 regulating synaptic membrane exocytosis 2 chr8 104898344 NM_014677 exon2 c.A941T p.K314I exonic 0.95 D ---+--- 1 CBWD3 COBW domain containing 3 chr9 70483219 NM_001024916 exon4 c.A399G p.I133M exonic 0.94 D --+---- 1 USP26 ubiquitin specific peptidase 26 chrX 132161080 NM_031907 exon1 c.G1169A p.C390Y exonic 0.93 D ---+--- 1 CA4 carbonic anhydrase IV hsa04964 Proximal tubule bicarbonate reclamation chr17 58234791 NM_000717 exon4 c.T272G p.M91R exonic 0.92 D +------1 RASA1 RAS p21 protein activator (GTPase activating protein) 1hsa04360 Axon guidance chr5 86672330 NM_002890 exon16 c.G2132A p.R711Q exonic 0.91 D +------1 OR10K1 olfactory receptor, family 10, subfamily K, member 1 hsa04740 Olfactory transduction chr1 158436238 NM_001004473 exon1 c.A887T p.E296V exonic 0.90 D +------1 AGAP4 ArfGAP with GTPase domain, ankyrin repeat and PH domain 4 chr10 46342692 NM_133446 exon1 c.G104T p.G35V exonic 0.89 D ----+-- 1 AGAP8 ArfGAP with GTPase domain, ankyrin repeat and PH domain 8 chr10 51246306 NM_001077686 exon1 c.G104T p.G35V exonic 0.89 D ----+-- 1 PODXL2 podocalyxin-like 2 chr3 127358244 NM_015720 exon2 c.C227T p.A76V exonic 0.89 D ---+--- 1 TMEM19 transmembrane protein 19 chr12 72094728 NM_018279 exon6 c.G964A p.A322T exonic 0.85 D ---+--- 1 VSTM1 V-set and transmembrane domain containing 1 chr19 54544312 NM_198481 exon9 c.C614G p.T205S exonic 0.85 D --+---- 1 RBMXL1 RNA binding motif protein, X-linked-like 1 chr1 89448924 NM_019610 exon2 c.A586G p.R196G exonic 0.85 P ------+ 1 ZSCAN18 zinc finger and SCAN domain containing 18 chr19 58600105 NM_001145544 exon2 c.G98C p.S33T exonic 0.82 P ---+--- 1 EVI2A ecotropic viral integration site 2A chr17 29645685 NM_014210 exon2 c.G347A p.S116N exonic 0.79 P +------1 TF transferrin chr3 133495944 NM_001063 exon16 c.C1924T p.R642W exonic 0.79 P +------1 GGTLC2 gamma-glutamyltransferase light chain 2 chr22 22989701 NM_199127 exon4 c.C451T p.P151S exonic 0.78 P +------1 HKDC1 hexokinase domain containing 1 chr10 70998850 NM_025130 exon5 c.C548T p.T183M exonic 0.75 P +------1 LRP1 low density lipoprotein receptor-related protein 1 hsa05010 Alzheimer's disease chr12 57592066 NM_002332 exon59 c.C9410T p.T3137M exonic 0.75 P -+----- 1 RABEPK Rab9 effector protein with kelch motifs chr9 127969901 NM_005833 exon3 c.T112C p.Y38H exonic 0.74 P +------1 AVIL advillin chr12 58201116 NM_006576 exon12 c.G1489A p.E497K exonic 0.73 P --+---- 1 PABPC3 poly(A) binding protein, cytoplasmic 3 chr13 25671837 NM_030979 exon1 c.C1501T p.R501C exonic 0.73 P -----+- 1 GALNT8 UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosamhsa01100 inyltransferaseMetabolic pathways8 chr12 4848436 NM_017417 exon3 c.A617G p.N206S exonic 0.72 P ----+-- 1 ARHGEF5 Rho guanine nucleotide exchange factor (GEF) 5 chr7 144061607 NM_005435 exon2 c.G1845C p.Q615H exonic 0.71 P +------1 PPIP5K1 diphosphoinositol pentakisphosphate kinase 1 chr15 43874306 NM_001130859 exon6 c.G662A p.R221H exonic 0.69 P -+----- 1 OR2T5 olfactory receptor, family 2, subfamily T, member 5 hsa04740 Olfactory transduction chr1 248652230 NM_001004697 exon1 c.C341T p.S114L exonic 0.66 P ------+ 1 ANKRD20A4 ankyrin repeat domain 20 family, member A4 chr9 69389964 NM_001098805 exon4 c.C518T p.A173V exonic 0.65 P ---+--- 1 ANKRD20A1 ankyrin repeat domain 20 family, member A1 chr9 67960920 NM_001012419 exon12 c.A1120G p.R374G exonic 0.62 P +------1 ANKRD20A2 ankyrin repeat domain 20 family, member A2 chr9 42402476 NM_001012419 exon12 c.A1120G p.R374G exonic 0.62 P +------1 POLK polymerase (DNA directed) kappa chr5 74892737 NM_016218 exon13 c.A2219G p.H740R exonic 0.62 P ---+--- 1 SLC26A3 solute carrier family 26 (anion exchanger), member 3 chr7 107415251 NM_000111 exon16 c.C1744G p.Q582E exonic 0.61 P ----+-- 1 EEF1A1 eukaryotic translation elongation factor 1 alpha 1 chr6 74229160 NM_001402 exon3 c.T224C p.I75T exonic 0.61 P +------1 ZNF546 zinc finger protein 546 chr19 40520471 NM_178544 exon7 c.C1294G p.R432G exonic 0.59 P -+----- 1 PABPC3 poly(A) binding protein, cytoplasmic 3 chr13 25671558 NM_030979 exon1 c.C1222T p.P408S exonic 0.56 P ----+-- 1 C2orf27B chromosome 2 open reading frame 27B chr2 132553128 NM_214461 exon3 c.G238C p.E80Q exonic 0.55 P +------1 C2orf27B chromosome 2 open reading frame 27B chr2 132553158 NM_214461 exon3 c.G208A p.E70K exonic 0.55 P +------1 MRPL21 mitochondrial ribosomal protein L21 chr11 68660884 NM_181514 exon5 c.A436G p.K146E exonic 0.54 P -+----- 1 ANKRD20A4 ankyrin repeat domain 20 family, member A4 chr9 69421913 NM_001098805 exon14 c.T1377A p.N459K exonic 0.50 P ---+--- 1 NUP214 nucleoporin 214kDa chr9 134073285 NM_005085 exon29 c.C4404G p.F1468L exonic 0.50 P ---+--- 1 TPTE transmembrane phosphatase with tensin homology chr21 10951395 NM_199260 exon8 c.T203C p.V68A exonic 0.49 P ---+--- 1 PPRC1 peroxisome proliferator-activated receptor gamma, coactivator-related 1 chr10 103908247 NM_015062 exon10 c.T4519C p.S1507P exonic 0.48 P ---+--- 1 TAF1L TAF1 RNA polymerase II, TATA box binding protein (TBP)-assochsa03022 iated factor,Basal 210kDa-like transcription factors chr9 32631680 NM_153809 exon1 c.C3898T p.L1300F exonic 0.47 P ---+--- 1 LRIG3 leucine-rich repeats and immunoglobulin-like domains 3 chr12 59271588 NM_001136051 exon15 c.G1950C p.K650N exonic 0.47 P ----+-- 1 RAB34 RAB34, member RAS oncogene family chr17 27041832 NM_001256278 exon8 c.C691T p.R231X stopgain 0.74 ---+--- 1 CT45A3 cancer/testis antigen family 45, member A3 chrX 134891279 NM_001017435 exon5 c.C523T p.R175X stopgain 0.59 ---+--- 1 AHCY adenosylhomocysteinase hsa01100 Metabolic pathways chr20 32878356 NM_001161766 exon8 c.770+1G>T splicing - + - - - - - 1 ANKRD20A1 ankyrin repeat domain 20 family, member A1 chr9 67934721 NM_032250 c.493-2A>G splicing - - + - - - - 1 ARAP2 ArfGAP with RhoGAP domain, ankyrin repeat and PH domainhsa04144 2 Endocytosis chr4 36160952 NM_015230 exon15 c.2617+1G>C splicing + ------1 CBWD3 COBW domain containing 3 chr9 70483186 NM_201453 exon5 c.430+2T>C splicing - - - - + - - 1 FAM157B family with sequence similarity 157, member B chr9 141106792 NM_001145249 exon1 c.155+1G>T splicing - - + - - - - 1 NBPF15 neuroblastoma breakpoint family, member 15 chr1 148589047 NM_001170755 exon15 c.1040+2T>C splicing ------+ 1 NFKBIZ nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, zeta chr3 101576028 NM_001005474 exon11 c.1635+1G>C splicing - - - - + - - 1 RSPO1 R-spondin 1 chr1 38077350 NM_001242910 exon8 c.1610-1A>C splicing - - - + - - - 1 RSPO1 R-spondin 1 chr1 38077351 NM_001242910 exon8 c.1610-2A>T splicing - - - + - - - 1 ZACN zinc activated ligand-gated ion channel chr17 74075645 NM_180990 exon2 c.222+1G>C) splicing + ------1 Supplementary table 1B. Variants detected in breast cancer-affected members of family 2 Gene Description KEGG Pathway ID KEGG Pathway Description Chr Position RefSeq ExonChange Func ESP6500 1000 Genome dbSNP137 Nucleotide Amino acid KAT6B K(lysine) acetyltransferase 6B chr10 76789311 NM_012330 exon18 c.C4729T p.R1577C exonic KAT6B K(lysine) acetyltransferase 6B chr10 76789128 NM_012330 exon18 c.G4546T p.D1516Y exonic DHX57 DEAH (Asp-Glu-Ala-Asp/His) box polypeptide 57 chr2 39053697 NM_198963 exon15 c.T2774A p.V925D exonic GALNT9 UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalhsa01100actosaminyltransferaseMetabolic 9 pathways chr12 132688190 NM_021808 exon3 c.G25A p.V9M exonic GOLGB1 golgin B1 chr3 121415657 NM_001256488 exon12 c.T3473C p.L1158P exonic CALB1 calbindin 1, 28kDa chr8 91078175 NM_004929 exon6 c.C401G p.A134G exonic BDH1 3-hydroxybutyrate dehydrogenase, type 1 hsa01100 Metabolic pathways chr3 197241273 NM_004051 exon6 c.G424A p.V142I exonic STARD5 StAR-related lipid transfer (START) domain containing 5 chr15 81611793 NM_181900 exon4 c.T287C p.L96P exonic TRIT1 tRNA isopentenyltransferase 1 hsa01100 Metabolic pathways chr1 40309790 NM_017646 exon10 c.G1217T p.G406V exonic RGPD5 RANBP2-like and GRIP domain containing 5 chr2 111291808 NM_005054 exon20 c.G4155T p.Q1385H exonic TSSK4 testis-specific serine kinase 4 chr14 24675721 NM_001184739 exon2 c.A232G p.K78E exonic NOTCH2 notch 2 hsa04330 Notch signaling pathway chr1 120459167 NM_024408 exon34 c.C6178T p.R2060C exonic ADC arginine decarboxylase hsa01100 Metabolic pathways chr1 33562455 NM_052998 exon9 c.C901G p.Q301E exonic RBMXL1 RNA binding motif protein, X-linked-like 1 chr1 89448924 NM_019610 exon2 c.A586G p.R196G exonic ITGA10 integrin, alpha 10 hsa05414 Dilated cardiomyopathy chr1 145527706 NM_003637 exon2 c.T146C p.V49A exonic NOMO2 NODAL modulator 2 chr16 18528552 NM_001004060 exon23 c.C2716T p.L906F exonic ADSS adenylosuccinate synthase hsa01100 Metabolic pathways chr1 244580979 NM_001126 exon10 c.T1021G p.L341V exonic ANKMY1 ankyrin repeat and MYND domain containing 1 chr2 241463723 NM_017844 exon6 c.G721A p.E241K exonic PSG11 pregnancy specific beta-1-glycoprotein 11 chr19 43514108 NM_203287 exon5 c.682+2T>G splicing CPSF3L cleavage and polyadenylation specific factor 3-like chr1 1256452 NM_001256463 exon2 c.G50T p.R17L exonic ENO3 enolase 3 (beta, muscle) hsa03018 RNA degradation chr17 4859900 NM_001193503 exon8 c.T971G p.V324G exonic MAPK7 mitogen-activated protein kinase 7 hsa04912 GnRH signaling pathway chr17 19284136 NM_139032 exon2 c.G197C p.R66P exonic APC2 adenomatosis polyposis coli 2 hsa05217 Basal cell carcinoma chr19 1460246 NM_005883 exon11 c.C1370T p.P457L exonic DUSP16 dual specificity phosphatase 16 hsa04010 MAPK signaling pathway chr12 12629837 NM_030640 exon7 c.G1928A p.R643Q exonic GBGT1 globoside alpha-1,3-N-acetylgalactosaminyltransferase 1 hsa01100 Metabolic pathways chr9 136030613 NM_021996 exon6 c.A311C p.Y104S exonic TRIO trio Rho guanine nucleotide exchange factor chr5 14397227 NM_007118 exon29 c.C4387G p.R1463G exonic BTBD11 BTB (POZ) domain containing 11 chr12 108008893 NM_001017523 exon5 c.C566T p.T189M exonic DCAF12 DDB1 and CUL4 associated factor 12 chr9 34088458 NM_015397 exon9 c.C1252T p.P418S exonic NBPF16 neuroblastoma breakpoint family, member 16 chr1 148739778 NM_001102663 exon2 c.T44C p.M15T exonic SNAP23 synaptosomal-associated protein, 23kDa hsa04130 SNARE interactions in vesicular transport chr15 42807545 NM_003825 exon5 c.T259C p.C87R exonic HOXA9 homeobox A9 chr7 27203292 NM_152739 exon2 c.T749G p.V250G exonic CDH18 cadherin 18, type 2 chr5 19612624 NM_001167667 exon6 c.C730G p.Q244E exonic KIF18A kinesin family member 18A chr11 28116341 NM_031217 exon3 c.C332G p.A111G exonic GAGE12D G antigen 12D chrX 49339734 NM_001098405 exon3 c.A289G p.M97V exonic PSMG1 proteasome (prosome, macropain) assembly chaperone 1 chr21 40551854 NM_003720 exon4 c.A452G p.E151G exonic SPDYE2 speedy/RINGO cell cycle regulator family member E2 chr7 102196464 NM_001031618 exon4 c.A497T p.E166V exonic EIF3F eukaryotic translation initiation factor 3, subunit F chr11 8016010 NM_003754 exon5 c.A691T p.M231L exonic RASA4 RAS p21 protein activator 4 chr7 102232889 NM_001079877 exon16 c.A1673G p.Q558R exonic TNXB tenascin XB hsa04512 ECM-receptor interaction chr6 32009879 NM_019105 exon42 c.G12373A p.E4125K exonic BAZ1A bromodomain adjacent to zinc finger domain, 1A chr14 35243615 NM_182648 exon18 c.A2819G p.E940G exonic TUBA3D tubulin, alpha 3d hsa05130 Pathogenic Escherichia coli infection chr2 132237750 NM_080386 exon4 c.G484A p.G162S exonic MLC1 megalencephalic leukoencephalopathy with subcortical cysts 1 chr22 50515853 NM_015166 exon6 c.G502A p.E168K exonic LPA lipoprotein, Lp(a) chr6 161067421 NM_005577 exon4 c.G216T p.L72F exonic UHRF2 ubiquitin-like with PHD and ring finger domains 2, E3 ubiquitin protein ligase chr9 6504651 NM_152896 exon15 c.A2222C p.Y741S exonic PRAMEF15 PRAME family member 15 chr1 13424057 NM_001010890 exon2 c.C55G p.L19V exonic OSBPL7 oxysterol binding protein-like 7 chr17 45886729 NM_145798 exon19 c.T1996C p.S666P exonic AMY1A amylase, alpha 1A (salivary) hsa01100 Metabolic pathways chr1 104201275 NM_001008218 exon5 c.C727A p.P243T exonic AMY1A amylase, alpha 1A (salivary) hsa01100 Metabolic pathways chr1 104295414 NM_001008218 exon5 c.C727A p.P243T exonic VCAN versican hsa04514 Cell adhesion molecules (CAMs) chr5 82817864 NM_001164098 exon7 c.G3739A p.D1247N exonic FRG2 FSHD region gene 2 chr4 190947917 NM_001005217 exon2 c.C182G p.S61W exonic OSBPL7 oxysterol binding protein-like 7 chr17 45897456 NM_145798 exon3 c.G82A p.E28K exonic PNN pinin, desmosome associated protein chr14 39650027 NM_002687 exon9 c.G1114A p.V372I exonic TEKT4 tektin 4 chr2 95542344 NM_144705 exon6 c.C1138T p.R380X stopgain PRAMEF13 PRAME family member 13 chr1 13450112 NM_001024661 exon3 c.T314A p.L105X stopgain B4GALNT2 beta-1,4-N-acetyl-galactosaminyl transferase 2 chr17 47246094 NM_001159387 exon10 c.C1147T p.Q383X stopgain AASS aminoadipate-semialdehyde synthase hsa01100 Metabolic pathways chr7 121766427 NM_005763 exon5 c.472+2T>G splicing ADA adenosine deaminase hsa05340 Primary immunodeficiency chr20 43264866 NM_000022 exon3 c.95+2T>G splicing ANKRD20A2 ankyrin repeat domain 20 family, member A2 chr9 43105566 NM_001012421 exon11 c.980-1G>A splicing CCDC144NL coiled-coil domain containing 144 family, N-terminal like chr17 20770017 NM_001004306 exon4 c.416-1G>A splicing CDAN1 codanin 1 chr15 43023407 NM_138477 exon13 c.1860_2T>G splicing DNAH14 dynein, axonemal, heavy chain 14 chr1 225569283 NM_001373 exon79 c.12771+2T>G splicing FAM157A family with sequence similarity 157, member A chr3 197879392 NM_001145248 exon1 c.155+1G>T splicing PSG3 pregnancy specific beta-1-glycoprotein 3 chr19 43228092 NM_021016 exon7 c.1327+2T>G splicing PSG5 pregnancy specific beta-1-glycoprotein 5 chr19 43674205 NM_001130014 exon6 c.1048+2T>G splicing SPANXA1 sperm protein associated with the nucleus, X-linked, family member A1 chrX 140672728 NM_013453 exon2 c.72+1G>T splicing UBE2Q2 ubiquitin-conjugating enzyme E2Q family member 2 hsa04120 Ubiquitin mediated proteolysis chr15 76136828 NM_001145335 exon1 c.132+2T>G splicing PolyPhen2 Distribution Frequency Score Prediction 1 2 3 4 5 6 0.96 D -+++++ 5 0.95 D -+++++ 5 0.96 D +++-++ 4 0.86 D ++++-- 4 1.00 D -+++-- 3 0.97 D -+-++- 3 0.94 D +++--+ 3 1.00 D +-+--- 2 1.00 D +-+--+ 2 1.00 D +-+--- 2 1.00 D ---++- 2 0.99 D XX+XX+ 2 0.89 D ---++- 2 0.85 P ++---- 2 0.84 P ++---- 2 0.83 P ---++- 2 0.71 P +-+--- 2 0.56 P -+-+-- 2 - - + - + - 2 1.00 D ---+-- 1 1.00 D +----- 1 1.00 D ----+- 1 1.00 D +----- 1 1.00 D ----+- 1 1.00 D ---+-- 1 1.00 D ---+-- 1 1.00 D +----- 1 1.00 D +----- 1 1.00 D ---+-- 1 1.00 D ---+-- 1 0.99 D ---+-- 1 0.99 D ----+- 1 0.99 D --+--- 1 0.99 D +----- 1 0.99 D -+---- 1 0.99 D --+--+ 1 0.98 D ----+- 1 0.96 D ---+-- 1 0.96 D -+---- 1 0.95 D --+--+ 1 0.95 D ---+-- 1 0.94 D -+---- 1 0.92 D +----- 1 0.92 D +----- 1 0.91 D -+---- 1 0.87 D --+--- 1 0.86 D ----+- 1 0.86 D ----+- 1 0.85 D --+--- 1 0.74 P ----+- 1 0.65 P +----- 1 0.55 P --+--- 1 0.54 -+---- 1 0.73 +----- 1 0.72 --+--- 1 + - - - - - 1 - - - + - - 1 - - - + - - 1 - - - + - - 1 + - - - - - 1 - - + - - - 1 - - - + - - 1 + - - - - - 1 - - + - - - 1 + - - - - - 1 - - - - + - 1 Supplementary table 1C. Variants detected in breast cancer-affected members of family 3 Gene Description KEGG Pathway ID KEGG Pathway Description Chr Position RefSeq ExonChange Func ESP6500 1000genome dbSNP137 PolyPhen 2 Distribution Frequency Nucleotide Amino acid Score Prediction 1 2 4 5 6 NBPF16 neuroblastoma breakpoint family, member 16 chr1 148756665 NM_001102663 exon16 c.G1994T p.G665V exonic 0.92 D +++++ 5 PRAMEF15 PRAME family member 15 chr1 13424057 NM_001010890 exon2 c.C55G p.L19V exonic 0.91 D -++++ 4 VWF von Willebrand factor hsa04610 Complement and coagulation cascades chr12 6132010 NM_000552 exon26 c.G3434A p.R1145H exonic 1.00 D ++--+ 3 FLAD1 flavin adenine dinucleotide synthetase 1 hsa01100 Metabolic pathways chr1 154962131 NM_025207 exon3 c.G1213A p.G405R exonic 1.00 D -+++- 3 ANKRD20A1 ankyrin repeat domain 20 family, member A1 chr9 67934747 NM_001012419 exon4 c.G517A p.A173T exonic 0.65 P +-++- 3 ACADVL acyl-CoA dehydrogenase, very long chain hsa01100 Metabolic pathways chr17 7123990 NM_001033859 exon3 c.C206A p.P69Q exonic 1.00 D +---+ 2 CELSR2 cadherin, EGF LAG seven-pass G-type receptor 2 chr1 109811375 NM_001408 exon18 c.C6491T p.T2164M exonic 1.00 D -+-+- 2 ATP13A2 ATPase type 13A2 chr1 17322553 NM_001141973 exon15 c.G1445A p.R482Q exonic 1.00 D +---+ 2 KIF25 kinesin family member 25 chr6 168434602 NM_005355 exon4 c.G208A p.G70R exonic 1.00 D +---+ 2 ADCY9 adenylate cyclase 9 hsa05414 Dilated cardiomyopathy chr16 4016224 NM_001116 exon11 c.G3614A p.R1205H exonic 1.00 D -+-+- 2 RPGR retinitis pigmentosa GTPase regulator chrX 38182703 NM_000328 exon2 c.G103T p.D35Y exonic 1.00 D +---+ 2 LRRC42 leucine rich repeat containing 42 chr1 54417799 NM_052940 exon2 c.C127T p.P43S exonic 1.00 D -++-- 2 HABP4 hyaluronan binding protein 4 chr9 99227674 NM_014282 exon3 c.G568C p.G190R exonic 0.99 D -+-+- 2 SLC9A1 solute carrier family 9, subfamily A, member 1 hsa04810 Regulation of actin cytoskeleton chr1 27432443 NM_003047 exon5 c.A1418C p.H473P exonic 0.98 D +---+ 2 NANP N-acetylneuraminic acid phosphatase hsa01100 Metabolic pathways chr20 25596725 NM_152667 exon2 c.A583G p.I195V exonic 0.98 D --++- 2 PHLDB2 pleckstrin homology-like domain, family B, member 2 chr3 111638003 NM_001134438 exon4 c.G1804A p.E602K exonic 0.98 D +---+ 2 ACSS3 acyl-CoA synthetase short-chain family member 3 hsa01100 Metabolic pathways chr12 81545780 NM_024560 exon7 c.G1003A p.V335M splicing 0.97 D +--+- 2 C20orf26 chromosome 20 open reading frame 26 chr20 20150086 NM_001167816 exon12 c.A1367G p.H456R exonic 0.97 D +---+ 2 SMOC1 SPARC related modular calcium binding 1 chr14 70459139 NM_001034852 exon6 c.G532A p.G178R exonic 0.96 D +---+ 2 TBC1D3 TBC1 domain family, member 3 chr17 36343973 NM_001123391 exon7 c.G410A p.R137K exonic 0.96 D -+-+- 2 MUC17 mucin 17, cell surface associated chr7 100684145 NM_001040105 exon3 c.G9448A p.E3150K exonic 0.96 D +---+ 2 ITGAX integrin, alpha X (complement component 3 receptor 4 subunit)hsa04810 Regulation of actin cytoskeleton chr16 31388396 NM_000887 exon22 c.A2701C p.S901R exonic 0.92 D --++- 2 COBLL1 cordon-bleu WH2 repeat protein-like 1 chr2 165552017 NM_014900 exon12 c.G1999C p.E667Q exonic 0.92 D -+-+- 2 PPP6R2 protein phosphatase 6, regulatory subunit 2 chr22 50857867 NM_001242898 exon8 c.C821A p.T274N exonic 0.90 D +---+ 2 DNAH5 dynein, axonemal, heavy chain 5 chr5 13859690 NM_001369 exon30 c.G4821T p.Q1607H exonic 0.89 D +---+ 2 HSD3B2 hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroidhsa01100 delta-isomerase 2 Metabolic pathways chr1 119964797 NM_000198 exon4 c.G673A p.V225I exonic 0.85 D +---+ 2 C1orf168 chromosome 1 open reading frame 168 chr1 57258333 NM_001004303 exon2 c.T153G p.N51K exonic 0.85 D -+-+- 2 CD180 CD180 molecule chr5 66478761 NM_005582 exon3 c.T1910C p.V637A exonic 0.84 P +---+ 2 SYNE1 spectrin repeat containing, nuclear envelope 1 chr6 152651397 NM_033071 exon77 c.C14210G p.T4737R exonic 0.80 P -+-+- 2 KIFAP3 kinesin-associated protein 3 chr1 169951982 NM_001204516 exon13 c.G1401T p.Q467H exonic 0.80 P -+--+ 2 WBP4 WW domain binding protein 4 chr13 41650305 NM_007187 exon8 c.G688T p.D230Y exonic 0.78 P +---+ 2 CTBP2 C-terminal binding protein 2 chr10 126682485 NM_022802 exon6 c.G2470A p.A824T exonic 0.76 P +-+-- 2 SLC35F5 solute carrier family 35, member F5 chr2 114476839 NM_025181 exon14 c.T1388C p.F463S exonic 0.74 P -+-+- 2 FBXO27 F-box protein 27 chr19 39521850 NM_178820 exon3 c.A475T p.S159C exonic 0.72 P +--+- 2 CTBP2 C-terminal binding protein 2 chr10 126681831 NM_022802 exon7 c.G2599C p.E867Q exonic 0.68 P -+--+ 2 C2orf27B chromosome 2 open reading frame 27B chr2 132553158 NM_214461 exon3 c.G208A p.E70K exonic 0.55 P +--+- 2 WBP4 WW domain binding protein 4 chr13 41650306 NM_007187 exon8 c.A689T p.D230V exonic 0.62 P +---+ 2 CTBP2 C-terminal binding protein 2 chr10 126682493 NM_022802 exon6 c.T2462G p.L821X stopgain 0.74 + - + - - 2 RASA4 RAS p21 protein activator 4 chr7 102232872 NM_001079877 exon16 c.C1690T p.Q564X stopgain 0.73 - + - + - 2 VWF von Willebrand factor hsa04610 Complement and coagulation cascades chr12 6132006 NM_000552 exon26 c.T3438G p.Y1146X stopgain 0.58 - + - - + 2 ANKRD20A1 ankyrin repeat domain 20 family, member A1 chr9 67938656 NM_001012419 exon6 c.C791G p.S264X stopgain 0.57 + + - - - 2 CBWD3 COBW domain containing 3 chr9 70483186 NM_201453 exon5 c.430+2T>C splicing - + - + - 2 MCTP2 multiple C2 domains, transmembrane 2 chr15 94945249 NM_018349 exon16 c.2085+1G>A splicing + - - - + 2 PHKB phosphorylase kinase, beta hsa04910 Insulin signaling pathway chr16 47628126 NM_000293 exon12 c.1204+1G>T splicing + + - - - 2 RGPD4 RANBP2-like and GRIP domain containing 4 chr2 108473216 NM_182588 exon9 c.G1067A p.G356E splicing - + - + - 2 DUSP11 dual specificity phosphatase 11 (RNA/RNP complex 1-interacting) chr2 74005460 NM_003584 exon2 c.C286T p.R96C exonic 1.00 D --+-- 1 AGPAT6 1-acylglycerol-3-phosphate O-acyltransferase 6 hsa01100 Metabolic pathways chr8 41467450 NM_178819 exon4 c.G512A p.R171Q exonic 1.00 D -+--- 1 AGAP4 ArfGAP with GTPase domain, ankyrin repeat and PH domain 4 chr10 46322549 NM_133446 exon7 c.G806A p.R269Q exonic 1.00 D -+--- 1 ZNF264 zinc finger protein 264 chr19 57723864 NM_003417 exon4 c.C1399T p.R467W exonic 1.00 D ----+ 1 USH2A Usher syndrome 2A (autosomal recessive, mild) chr1 215990391 NM_206933 exon48 c.G9518A p.C3173Y exonic 1.00 D ----+ 1 OBFC1 oligonucleotide/oligosaccharide-binding fold containing 1 chr10 105659892 NM_024928 exon5 c.G385A p.G129R exonic 1.00 D ----+ 1 ZNF217 zinc finger protein 217 chr20 52199316 NM_006526 exon1 c.A50G p.Y17C exonic 1.00 D -+--- 1 SLC2A7 solute carrier family 2 (facilitated glucose transporter), member 7 chr1 9067406 NM_207420 exon10 c.T1155G p.C385W exonic 1.00 D -+--- 1 AGXT2L2 5-phosphohydroxy-L-lysine phospho-lyase chr5 177651720 NM_153373 exon5 c.G424A p.G142S exonic 1.00 D ----+ 1 ELMOD2 ELMO/CED-12 domain containing 2 chr4 141446677 NM_153702 exon2 c.A95G p.Q32R exonic 1.00 D +---- 1 PRAMEF15 PRAME family member 15 chr1 13427820 NM_001010890 exon4 c.G1398C p.R466S exonic 1.00 D +---- 1 ESYT3 extended synaptotagmin-like protein 3 chr3 138187537 NM_031913 exon13 c.T1349C p.L450S exonic 1.00 D -+--- 1 FRG1 FSHD region gene 1 chr4 190883081 NM_004477 exon8 c.T734G p.L245R exonic 1.00 D ---+- 1 FAF1 Fas (TNFRSF6) associated factor 1 chr1 51253730 NM_007051 exon4 c.C309A p.F103L exonic 1.00 D +---- 1 PABPC3 poly(A) binding protein, cytoplasmic 3 chr13 25670703 NM_030979 exon1 c.G367T p.G123C exonic 1.00 D --+-- 1 FLG filaggrin chr1 152280685 NM_002016 exon3 c.G6677T p.G2226V exonic 1.00 D +---- 1 ITGAD integrin, alpha D hsa04810 Regulation of actin cytoskeleton chr16 31422835 NM_005353 exon14 c.C1704G p.S568R exonic 1.00 D -+--- 1 ABCA12 ATP-binding cassette, sub-family A (ABC1), member 12 hsa02010 ABC transporters chr2 215848533 NM_015657 exon21 c.A3266T p.K1089I exonic 1.00 D -+--- 1 PXK PX domain containing serine/threonine kinase chr3 58394655 NM_017771 exon14 c.C1235T p.P412L exonic 1.00 D --+-- 1 FKTN fukutin chr9 108366641 NM_006731 exon5 c.A515T p.H172L exonic 1.00 D +---- 1 RUFY1 RUN and FYVE domain containing 1 hsa04144 Endocytosis chr5 178996367 NM_001040451 exon4 c.G445T p.V149L exonic 1.00 D -+--- 1 FRG1 FSHD region gene 1 chr4 190883080 NM_004477 exon8 c.C733A p.L245M exonic 0.99 D ---+- 1 PNO1 partner of NOB1 homolog (S. cerevisiae) chr2 68389770 NM_020143 exon5 c.C595T p.R199W exonic 0.99 D --+-- 1 MYO1D myosin ID chr17 31065294 NM_015194 exon14 c.C1723G p.L575V exonic 0.99 D ----+ 1 GBF1 golgi brefeldin A resistant guanine nucleotide exchange factor 1 chr10 104130235 NM_001199378 exon28 c.G3506A p.R1169K splicing 0.99 D ---+- 1 TYRP1 tyrosinase-related protein 1 hsa04916 Melanogenesis chr9 12695728 NM_000550 exon3 c.T599G p.F200C exonic 0.98 D ----+ 1 PABPC3 poly(A) binding protein, cytoplasmic 3 chr13 25671451 NM_030979 exon1 c.A1115G p.E372G exonic 0.98 D ---+- 1 TEX35 testis expressed 35 chr1 178485777 NM_001170722 exon5 c.G268T p.D90Y exonic 0.98 D -+--- 1 CTBP2 C-terminal binding protein 2 chr10 126682484 NM_022802 exon6 c.C2471T p.A824V exonic 0.98 D --+-- 1 GIGYF2 GRB10 interacting GYF protein 2 chr2 233599926 NM_001103148 exon2 c.A19G p.T7A exonic 0.98 D +---- 1 NIN ninein (GSK3B interacting protein) chr14 51230649 NM_016350 exon15 c.G1669C p.E557Q exonic 0.98 D -+--- 1 IGSF10 immunoglobulin superfamily, member 10 chr3 151156180 NM_001178145 exon2 c.C250G p.Q84E exonic 0.98 D ---+- 1 MYRIP myosin VIIA and Rab interacting protein chr3 40208375 NM_015460 exon6 c.G589A p.V197M exonic 0.98 D -+--- 1 ASTN1 astrotactin 1 chr1 176926944 NM_004319 exon11 c.C1757T p.S586F exonic 0.98 D -+--- 1 TBC1D3B TBC1 domain family, member 3B chr17 34493880 NM_001001417 exon14 c.T1145C p.L382P exonic 0.98 D ----+ 1 KIF1B kinesin family member 1B chr1 10357101 NM_015074 exon19 c.C1870G p.Q624E exonic 0.96 D -+--- 1 MME membrane metallo-endopeptidase hsa05010 Alzheimer's disease chr3 154886385 NM_000902 exon19 c.T1885A p.F629I exonic 0.96 D -+--- 1 CSMD3 CUB and Sushi multiple domains 3 chr8 113314190 NM_052900 exon51 c.T7765C p.S2589P exonic 0.95 D ----+ 1 GALNT1 UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalhsa01100actosaminyltransferaseMetabolic 1 pathways chr18 33282877 NM_020474 exon9 c.C1316T p.T439M exonic 0.93 D +---- 1 WSCD2 WSC domain containing 2 chr12 108642084 NM_014653 exon9 c.C1662A p.N554K exonic 0.93 D --+-- 1 UBOX5 U-box domain containing 5 hsa04120 Ubiquitin mediated proteolysis chr20 3103004 NM_014948 exon3 c.G281T p.W94L exonic 0.93 D -+--- 1 MED13 mediator complex subunit 13 chr17 60030351 NM_005121 exon27 c.A6092G p.Y2031C exonic 0.91 D +---- 1 GPRIN1 G protein regulated inducer of neurite outgrowth 1 chr5 176026123 NM_052899 exon2 c.T713C p.L238S exonic 0.91 D ---+- 1 POTEB POTE ankyrin domain family, member B chr15 21071526 NM_207355 exon1 c.C85G p.H29D exonic 0.90 D ---+- 1 TBC1D3B TBC1 domain family, member 3B chr17 34493881 NM_001001417 exon14 c.C1144T p.L382F exonic 0.89 D ----+ 1 POTEB POTE ankyrin domain family, member B chr15 21071530 NM_207355 exon1 c.G81T p.W27C exonic 0.88 D +---- 1 RASA4 RAS p21 protein activator 4 chr7 102232745 NM_001079877 exon16 c.C1817T p.T606M exonic 0.88 D -+--- 1 ANO10 anoctamin 10 chr3 43607182 NM_001204833 exon6 c.T923C p.I308T exonic 0.85 D ---+- 1 REST RE1-silencing transcription factor hsa05016 Huntington's disease chr4 57797283 NM_001193508 exon4 c.G2259A p.M753I exonic 0.84 P ----+ 1 NOMO2 NODAL modulator 2 chr16 18528552 NM_001004060 exon23 c.C2716T p.L906F exonic 0.83 P --+-- 1 IGHMBP2 immunoglobulin mu binding protein 2 chr11 68678968 NM_002180 exon5 c.C608A p.A203E exonic 0.83 P -+--- 1 LACRT lacritin chr12 55025569 NM_033277 exon4 c.G308A p.G103E exonic 0.82 P +---- 1 ANKRD12 ankyrin repeat domain 12 chr18 9256621 NM_001083625 exon8 c.A3287G p.K1096R exonic 0.80 P +---- 1 NUP214 nucleoporin 214kDa chr9 134034842 NM_005085 exon18 c.G2509T p.D837Y exonic 0.79 P ---+- 1 METTL5 methyltransferase like 5 chr2 170677755 NM_014168 exon3 c.G253C p.D85H exonic 0.79 P ----+ 1 BCLAF1 BCL2-associated transcription factor 1 chr6 136588289 NM_001077441 exon11 c.G1903A p.A635T exonic 0.78 P +---- 1 FAM120A family with sequence similarity 120A chr9 96326682 NM_014612 exon18 c.G3217C p.A1073P exonic 0.77 P ----+ 1 LAMC3 laminin, gamma 3 hsa05222 Small cell lung cancer chr9 133943569 NM_006059 exon15 c.C2698T p.R900C exonic 0.75 P ----+ 1 FRG2 FSHD region gene 2 chr4 190947917 NM_001005217 exon2 c.C182G p.S61W exonic 0.74 P ----+ 1 DOCK5 dedicator of cytokinesis 5 chr8 25158140 NM_024940 exon9 c.A813G p.I271M exonic 0.73 P ----+ 1 ARHGEF35 Rho guanine nucleotide exchange factor (GEF) 35 chr7 143885401 NM_001003702 exon2 c.G76A p.A26T exonic 0.70 P ---+- 1 PABPC3 poly(A) binding protein, cytoplasmic 3 chr13 25670712 NM_030979 exon1 c.C376G p.L126V exonic 0.69 P --+-- 1 SP3 Sp3 transcription factor chr2 174820513 NM_001017371 exon2 c.G523C p.G175R exonic 0.68 P +---- 1 ACSL3 acyl-CoA synthetase long-chain family member 3 hsa04920 Adipocytokine signaling pathway chr2 223781134 NM_203372 exon4 c.A476C p.K159T exonic 0.67 P --+-- 1 HIST1H2AG histone cluster 1, H2ag hsa05322 Systemic lupus erythematosus chr6 27101016 NM_021064 exon1 c.C166G p.L56V exonic 0.65 P -+--- 1 IFT81 intraflagellar transport 81 homolog (Chlamydomonas) chr12 110573237 NM_001143779 exon7 c.A691T p.N231Y exonic 0.63 P --+-- 1 EEF1A1 eukaryotic translation elongation factor 1 alpha 1 chr6 74229160 NM_001402 exon3 c.T224C p.I75T exonic 0.61 P -+--- 1 GGTLC2 gamma-glutamyltransferase light chain 2 chr22 22988846 NM_199127 exon1 c.C31T p.R11W exonic 0.57 P -+--- 1 FLG filaggrin chr1 152278601 NM_002016 exon3 c.G8761A p.E2921K exonic 0.55 P ----+ 1 RGPD5 RANBP2-like and GRIP domain containing 5 chr2 111292658 NM_005054 exon20 c.A3305G p.E1102G exonic 0.49 P ---+- 1 RGPD5 RANBP2-like and GRIP domain containing 5 chr2 111304205 NM_005054 exon12 c.A1684G p.T562A exonic 0.47 P ----+ 1 CC2D1B coiled-coil and C2 domain containing 1B chr1 52823516 NM_032449 exon14 c.C1534G p.P512A exonic 0.47 P -+--- 1 OTOP2 otopetrin 2 chr17 72929521 NM_178160 exon7 c.G1570T p.E524X stopgain 0.74 - + - - - 1 NOMO3 NODAL modulator 3 chr16 16341285 NM_001004067 exon6 c.T543G p.Y181X stopgain 0.73 - - + - - 1 NOMO1 NODAL modulator 1 chr16 14942789 NM_014287 exon6 c.T543G p.Y181X stopgain 0.73 - - + - - 1 KRTAP5-7 keratin associated protein 5-7 chr11 71238747 NM_001012503 exon1 c.C401G p.S134X stopgain 0.73 - - - + - 1 INPP5B inositol polyphosphate-5-phosphatase, 75kDa hsa04070 Phosphatidylinositol signaling system chr1 38339753 NM_005540 exon18 c.T1863A p.C621X stopgain 0.60 - + - - - 1 FRG2C FSHD region gene 2 family, member C chr3 75713976 NM_001124759 exon2 c.C185G p.S62X stopgain 0.60 - - - - + 1 PRB1 proline-rich protein BstNI subfamily 1 chr12 11506775 NM_199353 exon3 c.C262T p.R88X stopgain 0.55 - + - - - 1 CBWD6 COBW domain containing 6 chr9 69255602 NM_001085457 exon5 c.430+2T>C splicing - + - - - 1 CLCA1 chloride channel accessory 1 hsa04740 Olfactory transduction chr1 86939560 NM_001285 exon3 c.451+1G>A splicing - - - - + 1 RASSF4 Ras association (RalGDS/AF-6) domain family member 4 chr10 45478112 NM_032023 exon4 c.281+1G>T splicing - + - - - 1 RGPD3 RANBP2-like and GRIP domain containing 3 chr2 107055633 NM_001144013 exon9 c.G1067A p.G356E splicing - + - - - 1 Table 1D. Shared variants in each of the three families validated by Sanger sequencing Gene Description Position RefSeqChange Type Distribution Frequency Nucleotide Amino acid Family 1 1 2 3 4 6 7 8 LRRC66 leucine rich repeat containing 66 chr4:52861746 NM_001024611 c.A1442T p.D481V exonic - - + + - + + 4 COL12A1 collagen, type XII, alpha 1 chr6:75864212 NM_004370 c.A3485C p.D1162A exonic - - + - + + - 3 ITPR2 inositol 1,4,5-trisphosphate receptor, chr12:26839489type 2 NM_002223 c.C1073T p.P358L exonic - - - - + + + 3 ABCC6 ATP-binding cassette, sub-family C (CFTR/MRP),chr16:16269844 memb NM_001171er 6 c.2591-1G>T - splicing--++--- 2 PINK1 PTEN induced putative kinase 1 chr1:20972051 NM_032409 c.960-2A>G - splicing - - + + - - - 2 RNF215 ring finger protein 215 chr22:30775768 NM_001017981 c.A1043G p.H348R exonic - - + + - - - 2 USP28 ubiquitin specific peptidase 28 chr11:113683049 NM_020886 c.A1921G p.S641G exonic - - + + - - - 2 ANKRD44 ankyrin repeat domain 44 chr2:197986226 NM_001195144 c.G736A p.A246T exonic - - - - + - + 2 AVIL advillin chr12:58197038 NM_006576 c.T1954C p.W652R exonic - - - -+-+ 2 NUP35 nucleoporin 35kDa chr2:184016246 NM_138285 c.G408C p.M136I exonic - - - - + - + 2 TEX15 testis expressed 15 chr8:30702074 NM_031271 c.C4460T p.T1487I exonic - - - - + - + 2 TIGD2 tigger transposable element derived 2chr4:90034310 NM_145715 c.C185T p.T62I exonic - - - - - + + 2 STK38 serine/threonine kinase 38 chr6:36507854 NM_007271 c.A126T p.E42D exonic - - - - -+ -+ - 2 RASA1 RAS p21 protein activator (GTPase activatingchr5:86672330 protein) 1 NM_002890 c.G2132A p.R711Q exonic -+ ------1 PEAK1 pseudopodium-enriched atypical kinasechr15:77472182 1 NM_024776 c.A2087C p.E696A exonic - -+ - - - - - 1 POLK polymerase (DNA directed) kappa chr5:74892737 NM_016218 c.A2219G p.H740R exonic - - - -+ - - - 1 Family 2 1 2 3 4 5 6 BDH1 3-hydroxybutyrate dehydrogenase, typechr3:197241273 1 NM_004051 c.G424A p.V142I exonic + + + - + + 5 KAT6B K(lysine) acetyltransferase 6B chr10:76789128 NM_001256468 c.G3997T p.D1333Y exonic - + + + + + 5 KAT6B K(lysine) acetyltransferase 6B chr10:76789311 NM_001256468 c.C4180T p.R1394C exonic - + + + + + 5 GALNT9 UDP-N-acetyl-alpha-D-galactosamine:polypeptidechr12:132688190 N-acetylgalactosaminyltransferase NM_021808 c.G25A 9 (GalNAc-T9) p.V9M exonic + + + + + - 5 GOLGB1 golgin B1 chr3:121415657 NM_001256488 c.T3473C p.L1158P exonic - + + + - - 3 CALB1 calbindin 1, 28kDa chr8:91078175 NM_004929 c.C401G p.A134G exonic - + - + + - 3 STARD5 StAR-related lipid transfer (START) domainchr15:81611793 containing 5 NM_181900 c.T287C p.L96P exonic + - + - - - 2 BAZ1A bromodomain adjacent to zinc finger chr14:35243615domain, 1A NM_182648 c.A2819G p.E940G exonic - - + - - + 2 NOTCH2 notch 2 chr1:120459167 NM_024408 c.C6178T p.R2060C exonic --+--+ 2 ADC arginine decarboxylase chr1:33562455 NM_052998 c.C901G p.Q301E exonic - - - + + - 2 TSSK4 testis-specific serine kinase 4 chr14:24675721 NM_001184739 c.A232G p.K78E exonic - - - + + - 2 DUSP16 dual specificity phosphatase 16 chr12:12629837 NM_030640 c.G1928A p.R643Q exonic - - - - -+ - 1 Family 3 1 2 4 5 6 CELSR2 cadherin, EGF LAG seven-pass G-typechr1:109811375 receptor 2 NM_001408 c.C6491T p.T2164M exonic - + + + - 3 FLAD1 flavin adenine dinucleotide synthetasechr1:154962131 1 NM_025207 c.G1213A p.G405R exonic - + + + - 3 LRRC42 leucine rich repeat containing 42 chr1:54417799 NM_052940 c.C127T p.P43S exonic - + + - - 2 ADCY9 adenylate cyclase 9 chr16:4016224 NM_001116 c.G3614A p.R1205H exonic - + - + - 2 C1orf168 chromosome 1 open reading frame 168chr1:57258333 NM_001004303 c.T153G p.N51K exonic - + - + - 2 COBLL1 cordon-bleu WH2 repeat protein-like chr2:1655520171 NM_014900 c.G1999C p.E667Q exonic - + - + - 2 HABP4 hyaluronan binding protein 4 chr9:99227674 NM_014282 c.G568C p.G190R exonic - + - + - 2 PHKB phosphorylase kinase, beta chr16:47628126 NM_000293 c.1204+1G>T - splicing + + - - - 2 NANP N-acetylneuraminic acid phosphatasechr20:25596725 NM_152667 c.A583G p.I195V exonic - - + + - 2 ACSS3 acyl-CoA synthetase short-chain familychr12:81545780 member 3 NM_024560 c.G1003A p.V335M exonic + - - + - 2 ACADVL acyl-CoA dehydrogenase, very long chainchr17:7123990 NM_001033859 c.C206A p.P69Q exonic + - - - + 2 ATP13A2 ATPase type 13A2 chr1:17322553 NM_001141973 c.G1445A p.R482Q exonic + - - - + 2 C20orf26 chromosome 20 open reading frame chr20:2015008626 NM_001167816 c.A1367G p.H456R exonic + - - - + 2 DNAH5 dynein, axonemal, heavy chain 5 chr5:13859690 NM_001369 c.G4821T p.Q1607H exonic + - - - + 2 HSD3B2 hydroxy-delta-5-steroid dehydrogenase,chr1:119964797 3 beta- and steroid NM_000198 delta-isomerase c.G673A 2 p.V225I exonic + - - - + 2 KIF25 kinesin family member 25 chr6:168434602 NM_005355 c.G208A p.G70R exonic + - - - + 2 MCTP2 multiple C2 domains, transmembranechr15:94945249 2 NM_018349 c.2085+1G>A - splicing + - - - + 2 PHLDB2 pleckstrin homology-like domain, familychr3:111638003 B, member 2 NM_001134438 c.G1804A p.E602K exonic + - - - + 2 PPP6R2 protein phosphatase 6, regulatory subunitchr22:50857867 2 NM_001242898 c.C821A p.T274N exonic + - - - + 2 RPGR retinitis pigmentosa GTPase regulatorchrX:38182703 NM_000328 c.G103T p.D35Y exonic + - - - + 2 SLC9A1 solute carrier family 9, subfamily A (NHE1,chr1:27432443 cation proton NM_003047antiporter 1), member c.A1418C 1 p.H473P exonic + - - - + 2 FBXO27 F-box protein 27 chr19:39521850 NM_178820 c.A475T p.S159C exonic + - - + - 2 DUSP11 dual specificity phosphatase 11 (RNA/RNPchr2:74005460 complex 1-interacting) NM_003584 c.C286T p.R96C exonic - - + - - 1 FAF1 Fas (TNFRSF6) associated factor 1 chr1:51253730 NM_007051 c.C309A p.F103L exonic + - - - - 1 BCLAF1 BCL2-associated transcription factor chr6:1365882891 NM_001077441 c.G1903A p.A635T exonic + - - - - 1 * 53 of 64 variants (84%) were validated by Sange sequencing.