Table 4. Candidate variants identified through whole exome sequencing in 7 multiplex families.
| Chr | Position | Ref | Alt | Gene | Full_Name | Alt Freq | PolyPhen | SIFT | CADD Cscore | Amino Acid Change | LOD | Family | Unaff | logFC | FDR |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 6631121 | C | T | TAS1R1 | taste receptor, type 1, member 1 | 0.0001 | + | 16.77 | NM_177540:exon2:c.C344T:p.T115M | 1.08 | D§ | 0 | N/A | N/A | |
| 1 | 15905363 | G | T | AGMAT | agmatine ureohydrolase (agmatinase) | 0.0026 | + | 15.62 | NM_024758:exon4:c.C711A:p.N237K | 0.83 | F | 1 | -0.127 | 0.952 | |
| 1 | 28206319 | G | A | C1orf38 | chromosome 1 open reading frame 38 | 0.0001 | + | + | 17.71 | NM_001105556:exon3:c.G400A:p.A134T | 0.57 | G§ | 0 | N/A | N/A |
| 1 | 28477192 | T | C | PTAFR | platelet-activating factor receptor | 0.0052 | + | + | 20.80 | NM_001164721:exon3:c.A341G:p.N114S | 0.57 | G§ | 0 | -0.506 | 0.867 |
| 1 | 33760820 | G | A | ZNF362 | zinc finger protein 362 | 0.0000 | + | 21.80 | NM_152493:exon8:c.G1060A:p.A354 | 0.85 | B§ | 1 | 0.336 | 0.784 | |
| 1 | 36638206 | G | A | MAP7D1 | MAP7 domain containing 1 | 0.0011 | + | + | 34.00 | NM_018067:exon4:c.G602A:p.R201Q | 0.47 | D§ | 0 | 0.157 | 0.792 |
| 1 | 111968011 | G | A | OVGP1 | oviductal glycoprotein 1, 120kDa | 0.0000 | + | + | 12.85 | NM_002557:exon4:c.C311T:p.T104I | 0.57 | G§ | 1 | -0.023 | 0.988 |
| 1 | 177899689 | C | A | SEC16B | SEC16 homolog B (S. cerevisiae) | 0.0010 | + | + | 21.60 | NM_033127:exon25:c.G3102T:p.Q1034H | 0.87 | C | 0 | N/A | N/A |
| 1 | 197072434 | T | A | ASPM | asp (abnormal spindle) homolog, microcephaly associated (Drosophila) | 0.0013 | + | 14.55 | NM_018136:exon18:c.A5947T:p.M1983L | 0.57 | G§ | 1 | 1.195 | 0.642 | |
| 1 | 204418411 | C | T | PIK3C2B | phosphoinositide-3-kinase, class 2, beta polypeptide | 0.0007 | + | + | 35.00 | NM_002646:exon15:c.G2248A:p.G750S | 0.57 | G§ | 1 | -0.505 | 0.672 |
| 1 | 212799290 | C | A | FAM71A | family with sequence similarity 71, member A | 0.0000 | + | 13.78 | NM_153606:exon1:c.C1071A:p.S357R | 0.57 | G§ | 1 | N/A | N/A | |
| 1 | 228290051 | T | G | C1orf35 | chromosome 1 open reading frame 35 | 0.0093 | + | 21.10 | NM_024319:exon5:c.A407C:p.E136A | -0.29 | A | 0 | -0.079 | 0.934 | |
| 2 | 10186509 | C | T | KLF11 | Kruppel-like factor 11 | 0.0003 | + | + | 14.69 | NM_001177718:exon2:c.C224T:p.P75L | 1.41 | A | 0 | -0.129 | 0.892 |
| 2 | 55825844 | A | G | SMEK2 | SMEK homolog 2, suppressor of mek1 (Dictyostelium) | 0.0026 | + | + | 23.90 | NM_001122964:exon4:c.T629C:p.F210S | 1.43 | E | 0 | -0.222 | 0.631 |
| 2 | 73718061 | A | G | ALMS1 | Alstrom syndrome 1 | 0.0000 | + | + | 12.02 | NM_015120:exon10:c.A8972G:p.D2991G | 1.13 | D§ | 0 | -0.264 | 0.749 |
| 2 | 74757348 | T | C | HTRA2 | HtrA serine peptidase 2 | 0.0030 | + | + | 11.98 | NM_013247:exon1:c.T215C:p.L72P | 1.43 | E | 0 | 0.267 | 0.595 |
| 2 | 161029157 | G | C | ITGB6 | integrin, beta 6 | 0.0001 | + | + | 17.45 | NM_000888:exon6:c.C844G:p.L282V | -0.84 | G | 1 | N/A | N/A |
| 3 | 126137556 | G | A | CCDC37 | coiled-coil domain containing 37 | 0.0052 | + | 12.36 | NM_182628:exon7:c.G589A:p.A197T | -0.84 | G | 2 | N/A | N/A | |
| 3 | 180334458 | C | T | CCDC39 | coiled-coil domain containing 39 | 0.0026 | + | 20.70 | NM_181426:exon18:c.G2432A:p.R811H | 0.22 | A | 1 | 0.167 | 0.882 | |
| 3 | 186508024 | A | C | RFC4 | replication factor C (activator 1) 4, 37kDa | 0.0000 | + | 12.98 | NM_002916:exon10:c.T903G:p.H301Q | 0.83 | F | 1 | 0.125 | 0.906 | |
| 4 | 106158134 | C | T | TET2 | tet oncogene family member 2 | 0.0000 | + | + | 12.41 | NM_017628:exon3:c.C3035T:p.P1012L | 0.57 | G§ | 1 | -0.231 | 0.878 |
| *4 | 106639176 | T | A | GSTCD | glutathione S-transferase, C-terminal domain containing | 0.0047 | + | 22.90 | NM_001031720:exon2:c.T406A:p.C136S | 0.57 | G§ | 1 | -0.199 | 0.781 | |
| 5 | 11018087 | T | C | CTNND2 | catenin (cadherin-associated protein), delta 2 (neural plakophilin-related arm-repeat protein) | 0.0000 | + | 25.80 | NM_001332:exon18:c.A3083G:p.K1028R | -0.29 | A | 0 | -1.940 | 0.401 | |
| 5 | 140801897 | C | T | PCDHGA11 | protocadherin gamma subfamily A, 11 | 0.0007 | + | 18.54 | NM_018914:exon1:c.C1103T:p.A368V | 0.57 | G | 1 | -0.587 | 0.624 | |
| 5 | 140955835 | C | T | DIAPH1 | diaphanous homolog 1 (Drosophila) | 0.0007 | + | 36.00 | NM_005219:exon14:c.G1423A:p.E475K | 0.57 | G | 1 | 0.344 | 0.612 | |
| 5 | 149901055 | G | A | NDST1 | N-deacetylase/N-sulfotransferase (heparan glucosaminyl) 1 | 0.0036 | + | 18.54 | NM_001543:exon2:c.G239A:p.R80H | 1.43 | E | 0 | -0.157 | 0.806 | |
| 5 | 157053610 | T | C | SOX30 | SRY (sex determining region Y)-box 30 | 0.0013 | + | 15.84 | NM_178424:exon5:c.A2000G:p.N667S | 0.83 | F | 0 | N/A | N/A | |
| 6 | 13316909 | G | T | TBC1D7 | TBC1 domain family, member 7 | 0.0042 | + | + | 23.60 | NM_001143965:exon5:c.C413A:p.A138D | 0.86 | G§ | 1 | -0.372 | 0.758 |
| 6 | 149856802 | C | T | PPIL4 | peptidylprolyl isomerase (cyclophilin)-like 4 | 0.0000 | + | + | 34.00 | NM_139126:exon5:c.G394A:p.G132S | -0.29 | A | 0 | 0.100 | 0.900 |
| 6 | 159420630 | A | T | RSPH3 | radial spoke 3 homolog (Chlamydomonas) | 0.0002 | + | + | 15.37 | NM_031924:exon1:c.T379A:p.C127S | 0.57 | G | 1 | -0.140 | 0.858 |
| 6 | 167709705 | G | A | UNC93A | unc-93 homolog A (C. elegans) | 0.0052 | + | 24.10 | NM_001143947:exon3:c.G455A:p.G152D | 0.85 | B | 1 | N/A | N/A | |
| 6 | 168317794 | A | C | MLLT4 | myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 4 | 0.0000 | + | + | 26.90 | NM_001207008:exon18:c.A2522C:p.K841T | 0.57 | G§ | 1 | -0.150 | 0.884 |
| 8 | 72958750 | T | A | TRPA1 | transient receptor potential cation channel, subfamily A, member 1 | 0.0000 | + | 14.64 | NM_007332:exon17:c.A2059T:p.N687Y | -0.96 | G | 0 | N/A | N/A | |
| 9 | 21166077 | T | C | IFNA21 | interferon, alpha 21 | 0.0002 | + | 10.42 | NM_002175:exon1:c.A535G:p.K179E | 1.12 | D§ | 0 | N/A | N/A | |
| 9 | 35404008 | G | A | UNC13B | unc-13 homolog B (C. elegans) | 0.0006 | + | + | 34.00 | NM_006377:exon39:c.G4754A:p.R1585H | 0.83 | F | 1 | -0.377 | 0.658 |
| 10 | 13240791 | C | A | MCM10 | minichromosome maintenance complex component 10 | 0.0049 | + | 17.17 | NM_018518:exon16:c.C2222A:p.T741K, | 0.85 | B | 1 | 1.318 | 0.563 | |
| 10 | 47087309 | G | C | PPYR1 | pancreatic polypeptide receptor 1 | 0.0000 | + | + | 15.45 | NM_005972:exon3:c.G526C:p.A176P | 0.57 | G§ | 1 | N/A | N/A |
| 10 | 82187167 | G | A | C10orf58 | chromosome 10 open reading frame 58 | 0.0013 | + | 36.00 | NM_032333:exon5:c.G491A:p.R164Q | 0.56 | G | 1 | N/A | N/A | |
| 10 | 105218301 | C | G | CALHM1 | calcium homeostasis modulator 1 | 0.0001 | + | 16.88 | NM_001001412:exon1:c.G208C:p.V70L | -0.29 | A | 1 | N/A | N/A | |
| 10 | 105727572 | C | G | SLK | FYN oncogene related to SRC, FGR, YES | 0.0000 | + | + | 20.60 | NM_014720:exon1:c.C69G:p.H23Q | -0.29 | A | 1 | 0.182 | 0.774 |
| ǂ10 | 105797397 | G | A | COL17A1 | collagen, type XVII, alpha 1 | 0.0005 | + | 14.75 | NM_000494:exon46:c.C3205T:p.R1069W | 0.57 | G | 1 | N/A | N/A | |
| 10 | 105893436 | T | G | WDR96 | WD repeat domain 96 | 0.0005 | + | 23.90 | NM_025145:exon35:c.A4538C:p.D1513A | -0.29 | A | 1 | 0.048 | 0.988 | |
| 11 | 400124 | C | G | PKP3 | plakophilin 3 | 0.0013 | + | + | 12.37 | NM_007183:exon6:c.C1431G:p.N477K | -0.71 | G§ | 0 | N/A | N/A |
| 11 | 73074872 | G | A | ARHGEF17 | Rho guanine nucleotide exchange factor (GEF) 17 | 0.0003 | + | + | 18.47 | NM_014786:exon16:c.G5327A:p.C1776Y | 1.13 | D§ | 0 | 0.162 | 0.931 |
| 11 | 108277861 | C | T | C11orf65 | chromosome 11 open reading frame 65 | 0.0064 | + | + | 21.30 | NM_152587:exon4:c.G190A:p.A64T | 1.13 | C | 1 | N/A | N/A |
| 11 | 124742851 | G | A | ROBO3 | roundabout, axon guidance receptor, homolog 3 (Drosophila) | 0.0004 | + | + | 20.20 | NM_022370:exon9:c.G1402A:p.V468M | 1.31 | A | 0 | -0.019 | 0.993 |
| 11 | 126147035 | T | G | FOXRED1 | FAD-dependent oxidoreductase domain containing 1 | 0.0013 | + | + | 18.40 | NM_017547:exon10:c.T1171G:p.L391V | -0.58 | F | 1 | -0.152 | 0.815 |
| ǂ12 | 2968094 | G | T | FOXM1 | forkhead box M1 | 0.0000 | + | + | 13.37 | NM_202003:exon8:c.C1957A:p.P653T | 0.29 | D§ | 0 | 0.885 | 0.615 |
| *12 | 12630140 | T | G | DUSP16 | dual specificity phosphatase 16 | 0.0026 | + | 16.34 | NM_030640:exon7:c.A1625C:p.D542A | -0.69 | B§ | 2 | -0.324 | 0.686 | |
| *12 | 49498284 | T | G | LMBR1L | limb region 1 homolog (mouse)-like | 0.0040 | + | 16.10 | NM_018113:exon5:c.A382C:p.M128L | 0.83 | F | 2 | 0.156 | 0.824 | |
| 12 | 56335802 | T | C | DGKA | diacylglycerol kinase, alpha 80kDa | 0.0000 | + | 17.40 | NM_001345:exon16:c.T1271C:p.V424A | 1.11 | D | 0 | 0.551 | 0.544 | |
| *12 | 96374381 | C | A | HAL | histidine ammonia-lyase | 0.0006 | + | + | 25.70 | NM_002108:exon17:c.G1472T:p.G491V | 1.14 | D§ | 1 | -0.479 | 0.922 |
| 12 | 126139069 | C | T | TMEM132B | transmembrane protein 132B | 0.0002 | + | + | 10.88 | NM_052907:exon9:c.C3050T:p.S1017L | 1.14 | D | 0 | -2.626 | 0.023 |
| 15 | 75014793 | T | A | CYP1A1 | cytochrome P450, family 1, subfamily A, polypeptide 1 | 0.0003 | + | + | 14.09 | NM_000499:exon2:c.A646T:p.S216C | 0.83 | F | 1 | N/A | N/A |
| 16 | 449449 | G | A | NME4 | non-metastatic cells 4, protein expressed in | 0.0000 | + | 11.74 | NM_005009:exon3:c.G296A:p.R99H | 0.85 | B§ | 1 | -0.076 | 0.943 | |
| *16 | 2133701 | G | A | TSC2 | tuberous sclerosis 2 | 0.0040 | + | 12.84 | NM_001114382:exon32:c.G3820A:p.A1274T | 0.85 | B§ | 1 | -0.229 | 0.658 | |
| 16 | 11785220 | G | A | TXNDC11 | thioredoxin domain containing 11 | 0.0014 | + | 18.28 | NM_015914:exon8:c.C1826T:p.A609V | 0.85 | B§ | 1 | 0.134 | 0.896 | |
| 16 | 20796338 | G | A | ACSM3 | acyl-CoA synthetase medium-chain family member 3 | 0.0013 | + | + | 22.00 | NM_005622:exon8:c.G1052A:p.S351N | 0.57 | G | 0 | 0.751 | 0.496 |
| 16 | 53321892 | A | G | CHD9 | chromodomain helicase DNA binding protein 9 | 0.0076 | + | 18.22 | NM_025134:exon27:c.A5213G:p.K1738R | 0.65 | G | 0 | 0.095 | 0.910 | |
| 17 | 5425076 | A | G | NLRP1 | NLR family, pyrin domain containing 1 | 0.0042 | + | 10.35 | NM_033007:exon12:c.T3461C:p.M1154T | -0.56 | D§ | 0 | 0.293 | 0.727 | |
| 17 | 48762223 | G | A | ABCC3 | ATP-binding cassette, sub-family C (CFTR/MRP), member 3 | 0.0013 | + | + | 22.70 | NM_003786:exon29:c.G4267A:p.G1423R | 0.85 | B§ | 0 | -0.043 | 0.994 |
| 17 | 61432613 | T | A | TANC2 | tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2 | 0.0000 | + | + | 25.00 | NM_025185:exon12:c.T2222A:p.F741Y | 0.85 | B§ | 0 | -0.213 | 0.859 |
| 19 | 11598418 | G | A | ZNF653 | zinc finger protein 653 | 0.0000 | + | 16.16 | NM_138783:exon4:c.C860T:p.A287V | 1.41 | A | 1 | 0.168 | 0.829 | |
| 19 | 13226094 | G | A | TRMT1 | TRM1 tRNA methyltransferase 1 homolog (S. cerevisiae) | 0.0002 | + | + | 20.70 | NM_017722:exon4:c.C640T:p.R214W | 1.41 | A | 1 | 0.222 | 0.737 |
| 19 | 57175814 | C | G | ZNF835 | zinc finger protein 835 | 0.0009 | + | 18.91 | NM_001005850:exon2:c.G753C:p.E251D | 0.86 | G | 1 | -0.797 | 0.556 | |
| 19 | 57723459 | C | T | ZNF264 | zinc finger protein 264 | 0.0000 | + | + | 11.70 | NM_003417:exon4:c.C994T:p.R332W | 0.86 | G | 1 | -0.132 | 0.882 |
| 20 | 44463002 | A | G | SNX21 | sorting nexin family member 21 | 0.0000 | + | 22.20 | NM_152897:exon2:c.A184G:p.S62G | 0.85 | B§ | 1 | -0.220 | 0.797 | |
| 6 | 153312343 | TTTTA | T | MTRF1L | mitochondrial translational release factor 1-like | 0.0000 | NA | + (SIFT-INDEL) | 14.77 | NM_019041:exon6:c.915_918del:p.305_306del | 0.57 | G | 1 | -0.095 | 0.924 |
Ref = reference allele, Alt = alternate allele. Alt Freq = alternate allele frequency (consensus frequency for the alternate allele from 1000 Genomes and/or Exome Sequencing Project, as described in the Methods), LOD = maximum LOD score for linkage markers found within a 10Mb window of the sequencing variant, Unaff = number of sequenced unaffected individuals who carry the variant, logFC = log fold change of expression differential (N/A indicates no expression data is available for the gene), FDR = false discovery rate-adjusted p-value. All variants are predicted to be non-synonymous exonic variants except the deletion at the end of the Table. A plus sign (+) denotes a damaging prediction. For variants segregating in families B, D, or G, a (§) indicates that variant was also shared by an individual in the same family with a probable or possible IA or an abdominal aortic aneurysm.