Supplemental Table 1 –Phenotypes considered “potentially diagnosable” by cytogenomic microarray8 (From Riggs’s Original Paper)

Phenotype / Associated Gene/Genomic Region / Clinical Management Issues? / Level of Evidence / Coordinates (GRC 37/hg19) / Management Implications
Phenotypes associated with loss of function mechanism
22q11.2 deletion syndrome / 22q11.2 / Yes / Level 1 / chr22:18661725-21561514 / R, D, S, M, L
46, XY complete gonadal dysgenesis or disorders of sex development / SRY / Yes / Level 1 / chrY:2654896-2655792 / R, D, S, M, L
46, XY sex reversal / NR5A1 / Yes / Level 1 / chr9:127243515-127269699 / R, D, M
Androgen Insensitivity Syndrome / AR / Yes / Level 1 / chrX:66763874-66944119 / R, D, O
APC-Associated Polyposis / APC / Yes / Level 1 / chr5:112043218-112181936 / R, P, S, M
Duchenne/Becker Muscular Dystrophy / DMD / Yes / Level 1 / chrX:31137345-33357726 / R, D, S, M, L
Fabry Disease / GLA / Yes / Level 1 / chrX:100652779-100663001 / R, D, M, L, O
Familial Pulmonary Fibrosis / TERT / Yes / Level 1 / chr5:1253282-1295162 / R, D, S, L
Hemophilia A / F8 / Yes / Level 1 / chrX:154064063-154250998 / R, D, M, L
Hereditary Breast and Ovarian Cancer / BRCA2 / Yes / Level 1 / chr13:32889617-32973809 / R, D, S, P
Heritable Pulmonary Arterial Hypertension / BMPR2 / Yes / Level 1 / chr2:203241050-203432474 / R, D, S, P, M, L
Leri-Weill Dyschondrosteosis / Xp22.33 / Yes / Level 1 / chrX:585078-620146 / R, D, S, P, L
Li-Fraumeni Syndrome / TP53 / Yes / Level 1 / chr17:7571720-7590863 / R, S, L
Long QT Syndrome 1 / KCNQ1 / Yes / Level 1 / chr11:2466221-2870340 / R, D
Marfan Syndrome / FBN1 / Yes / Level 1 / chr15:48700503-48937985 / R, D, S, M, L
Neurofibromatosis Type 1 / 17q11.2 / Yes / Level 1 / chr17:29162822-30218667 / R, D, S
Neurofibromatosis Type 1 / NF1 / Yes / Level 1 / chr17:29421945-29704695 / R, D, S
Prader Willi Syndrome / 15q11.2q13.1 / Yes / Level 1 / chr15:22876632-28557186 / R, D, S, M, L
SHOX-related haploinsufficiency disorders / SHOX / Yes / Level 1 / chrX:585078-620146 / R, D, P, S, M, L
Williams Syndrome / 7q11.23 / Yes / Level 1 / chr7:72744454-74142513 / R, D, S, M, L
1p36 Deletion Syndrome / 1p36 / Yes / Level 2 / chr1:834083-5408761 / R, D, S, M
1q21.1 Deletion Syndrome / 1q21.1 / Yes / Level 2 / chr1:146577486-147394506 / R, D, S, L
2q37 Deletion Syndrome / 2q37 / Yes / Level 2 / chr2:239954693-242930600 / R, D, L
9q22.3 microdeletion / Basal cell nevus syndrome / 9q22.3 / Yes / Level 2 / chr9:91928301 -98431061 / R, D, P, L
15q13.3 Deletion Syndrome / 15q13.3 / Yes / Level 2 / chr15:30769995-32701482 / R, D
15q24 microdeletion / 15q24.2 / Yes / Level 2 / chr15:74377174-76162277 / R, D, P
16p11.2 Deletion Syndrome / 16p11.2 / Yes / Level 2 / chr16:29649996-30199855 / R, S
22q11.2-related cardiac phenotype / TBX1 / Yes / Level 2 / chr22:19744226-19771116 / R, D, S
Aniridia / PAX6 / Yes / Level 2 / chr11:31806340-31839509 / R, S
AHC with complex glycerol kinase deficiency (contiguous gene disorder) / NR0B1 / Yes / Level 2 / chrX:30322539-30327495 / R, D, S, M, L
Alagille Syndrome / JAG1 / Yes / Level 2 / chr20:10618332-10654694 / R, D, S, P, M, L
Alport Syndrome / COL4A5 / Yes / Level 2 / chrX:107683154-107940775 / R, D, S, M
Angelman Syndrome / UBE3A / Yes / Level 2 / chr15:25582396-25684128 / R, D, S, M, L
Angelman Syndrome / 15q11.2q13.1 / Yes / Level 2 / chr15:22876632-28557186 / R, D, S, M, L
Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate / TP63 / Yes / Level 2 / chr3:189349216-189615068 / R, S, L
Anophthalmia / OTX2 / Yes / Level 2 / chr14:57267425-57277184 / D, S
Anophthalmia / SIX6 / Yes / Level 2 / chr14:60975938-60978525 / D, S, P, L
Arts Syndrome / PRPS1 / Yes / Level 2 / chrX:106871654-106894256 / R, D, S, P
ATRX Syndrome / ATRX / Yes / Level 2 / chrX:76760356-77041719 / R, P, M
Beckwith-Wiedemann Syndrome / CDKN1C / Yes / Level 2 / chr11:2904448-2906995 / R, D, S
Blepharophimosis, Ptosis, and Epicanthus Inversus / FOXL2 / Yes / Level 2 / chr3:138663066-138665982 / R, D, S, M
Branchiootic Syndrome 3 / SIX1 / Yes / Level 2 / chr14:61111417-61116155 / R, D, S, M
Branchiootorenal Syndrome / EYA1 / Yes / Level 2 / chr8:72109668-72274467 / R, D, S, M
Campomelic Dysplasia / SOX9 / Yes / Level 2 / chr17:70117161-70122561 / R, D, S, P
Charcot-Marie-Tooth Disease, Type 5 / PRPS1 / Yes / Level 2 / chrX:106871654-106894256 / R, D, S, M
CHARGE Syndrome / CHD7 / Yes / Level 2 / chr8:61591339-61779465 / R, D, S
Chondrodysplasia Punctata / ARSE / Yes / Level 2 / chrX:2852673-2882494 / R, D, S, P
Cleidocranial Dysostosis / RUNX2 / Yes / Level 2 / chr6:45296054-45518819 / R, D, S, P, M, L
Coffin-Lowry Syndrome / RPS6KA3 / Yes / Level 2 / chrX:20168029-20284750 / R, D, S, P, L
Congenital adrenal hypoplasia with hypogonadotrophic hypogonadism / NR0B1 / Yes / Level 2 / chrX:30322539-30327495 / R, D, S, M, L
Cornelia de Lange Syndrome / NIPBL / Yes / Level 2 / chr5:36876861-37065921 / R, D, S
Cri-du-Chat Syndrome / 5p15.2 / Yes / Level 2 / chr5:37693-11347262 / R, D, S
Deafness-Dystonia-Optic Neuropathy Syndrome / TIMM8A / Yes / Level 2 / chrX:100600644-100603957 / R, D, S, M
Diamond-Blackfan Anemia / RPS19 / Yes / Level 2 / chr19:42363988-42375484 / R, D, S, M
Early Onset Familial Alzheimer Disease / APP / Yes / Level 2 / chr21:27252861-27543138 / R, M
Enlarged Parietal Foramina/Cranium Bifidum / MSX2 / Yes / Level 2 / chr5:174151575-174157902 / R, L
Exudative Retinopathy / FZD4 / Yes / Level 2 / chr11:86656721-86666433 / R, P, S
Fanconi Anemia, Type B / FANCB / Yes / Level 2 / chrX:14861529-14891184 / R, D, P, S, M, L
Feingold Syndrome / MYCN / Yes / Level 2 / chr2:16080683-16087129 / R, D, P, M
Focal dermal hypoplasia / PORCN / Yes / Level 2 / chrX:48367371-48379202 / R, D, P, S, M, L
Fragile-X Syndrome / FMR1 / Yes / Level 2 / chrX:146993469-147032647 / R, D, M
Greig Cephalopolysyndactyly / GLI3 / Yes / Level 2 / chr7:42000547-42276618 / R, S
Hemophilia B / F9 / Yes / Level 2 / chrX:138612895-138645617 / R, D, M, L
Hereditary Multiple Osteochondromas / EXT1 / Yes / Level 2 / chr8:118811602-119124058 / R, D, P
Hereditary Multiple Osteochondromas / EXT2 / Yes / Level 2 / chr11:44117099-44266980 / R, D, P
Hereditary Neuropathy with Liability to Pressure Palsies / 17p12 / Yes / Level 2 / chr17:14097914-15422955 / R, M, P, L
Hereditary Neuropathy with Liability to Pressure Palsies / PMP22 / Yes / Level 2 / chr17:15133096-15168644 / R, M, P, L
Hirschsprung Disease / EDNRB / Yes / Level 2 / chr13:78469616-78492966 / R, D, P
Hirschsprung Disease / RET / Yes / Level 2 / chr10:43572517-43625799 / R, D, P
Holoprosencephaly / GLI2 / Yes / Level 2 / chr2:121554867-121750229 / R, D, S, M
Holoprosencephaly / SHH / Yes / Level 2 / chr7:155595558-155604967 / R, D, S, M
Holoprosencephaly / SIX3 / Yes / Level 2 / chr2:45169037-45173216 / R, D, S, M
Holoprosencephaly / TGIF1 / Yes / Level 2 / chr18:3412072-3458409 / R, D, S, M
Holoprosencephaly / ZIC2 / Yes / Level 2 / chr13:100634319-100639019 / R, D, S, M
Holt-Oram Syndrome / TBX5 / Yes / Level 2 / chr12:114791735-114846247 / R, D, S, P, M
Incontinentia Pigmenti / IKBKG / Yes / Level 2 / chrX:153770459-153793261 / R, D, S, M, L
Juvenile Polyposis Syndrome / SMAD4 / Yes / Level 2 / chr18:48556583-48611412 / R, D, S, P, M
Juvenile Polyposis Syndrome / BMPR1A / Yes / Level 2 / chr10:88516396-88684945 / R, D, S, P, M
Kallmann Syndrome / FGFR1 / Yes / Level 2 / chr8:38268656-38326352 / R, D, S, P, M
Kallmann Syndrome / KAL1 / Yes / Level 2 / chrX:8496915-8700227 / R, D, S, P, M
Kleefstra Syndrome / 9q34 / Yes / Level 2 / chr9:140403363-141153431 / R, D, S
Kleefstra Syndrome / EHMT1 / Yes / Level 2 / chr9:140605417-140730579 / R, D, S
Lesch-Nyhan Syndrome / HPRT1 / Yes / Level 2 / chrX:133594175-133634698 / R, D, S, P, M, L
Lissencephaly/Subcortical Band Heterotopia / DCX / Yes / Level 2 / chrX:110537007-110655406 / R, D, S
Loeyz-Dietz Syndrome / TGFBR1 / Yes / Level 2 / chr9:101867412-101916474 / R, D, S, P, M, L
Loeyz-Dietz Syndrome / TGFBR2 / Yes / Level 2 / chr3:30647994-30735634 / R, D, S, P, M, L
Lowe Syndrome (oculocerebrorenal syndrome)/Dent Disease / OCRL / Yes / Level 2 / chrX:128674252-128726533 / R, D, S, M, L
MAPT-related disorders / MAPT / Yes / Level 2 / chr17:43971748-44105700 / R, D, M
Menkes Disease / ATP7A / Yes / Level 2 / chrX:77166194-77305892 / R, D, M
Miller-Dieker Syndrome / 17p13.3 / Yes / Level 2 / chr17:1182956-2588909 / R, D
Miller-Dieker Syndrome / PAFAH1B1 / Yes / Level 2 / chr17:2496923-2588909 / R, D
Mowat-Wilson Syndrome / ZEB2 / Yes / Level 2 / chr2:145141942-145277958 / R, D, S, P
Mucopolysaccharidosis Type II (Hunter Syndrome) / IDS / Yes / Level 2 / chrX:148560295-148586884 / R, D, S, P, M
Myoclonus-Dystonia / SGCE / Yes / Level 2 / chr7:94214536-94285521 / R, D, P, M, L
Nail Patella Syndrome / LMX1B / Yes / Level 2 / chr9:129376722-129463311 / R, D, P, S, M
NDP-Related Retinopathies (Norrie Disease) / NDP / Yes / Level 2 / chrX:43808022-43832921 / R, P, S, L
Nephrogenic Diabetes Insipidus / AVPR2 / Yes / Level 2 / chrX:153167985-153172620 / R, D, P, S, M, L
Neurofibromatosis Type 2 / NF2 / Yes / Level 2 / chr22:29999545-30094589 / R, D, P, S, L
Nevoid basal cell carcinoma syndrome / PTCH1 / Yes / Level 2 / chr9:98205264-98279247 / R, D, P, S, L
Oral-Facial-Digital Syndrome / OFD1 / Yes / Level 2 / chrX:13752832-13787480 / R, D, P, S
Osteogenesis Imperfecta / COL1A1 / Yes / Level 2 / chr17:48261457-48279000 / R, D, P, M, L
Enlarged Parietal Foramina / ALX4 / Yes / Level 2 / chr11:44282278-44331716 / R, D, P, L
Pelizaeus-Merzbacher Disease / PLP1 / Yes / Level 2 / chrX:103031439-103047548 / R, D, P
Phelan-McDermid Syndrome / 22q13.3 / Yes / Level 2 / chr22:51045516-51178945 / R, D, S, L
Polycystic kidney Disease / PKD1 / Yes / Level 2 / chr16:2138711-2185899 / R, D, P, S, M, L
Polycystic Kidney Disease / PKD2 / Yes / Level 2 / chr4:88928820-88998929 / R, D, P, S, M, L
Potocki-Shaffer Syndrome / 11p11.2 / Yes / Level 2 / chr11:43985277-46064560 / R, D, S
PTEN Hamartoma Tumor Syndrome / PTEN / Yes / Level 2 / chr10:89623195-89728532 / R, D, P, S
Retinoblastoma / RB1 / Yes / Level 2 / chr13:48877883-49056026 / R, D, P, S, L
Retinoschisis / RS1 / Yes / Level 2 / chrX:18657808-18690223 / R, D, P, S, L
Rett syndrome and related disorders / MECP2 / Yes / Level 2 / chrX:153287264-153363188 / R, D, S, M
Rubinstein Taybi Syndrome / CREBBP / Yes / Level 2 / chr16:3775056-3930121 / R, D, P
Saethre-Chotzen Syndrome / TWIST1 / Yes / Level 2 / chr7:19155091-19157295 / R, D, P, S
SALL4-related disorders / SALL4 / Yes / Level 2 / chr20:50400581-50419048 / R, D, P, S, M
SCN1A-related seizure disorders / SCN1A / Yes / Level 2 / chr2:166845670-166930149 / R, D, M, L
Sensorineural hearing loss (Autosomal Dominant) / GJB2 / Yes / Level 2 / chr13:20761602-20767114 / R, D, P, L
Simpson-Golabi-Behmel Syndrome, Type 1 / GPC3 / Yes / Level 2 / chrX:132669773-133119673 / R, D, P, S
Smith Magenis / 17p11.2 / Yes / Level 2 / chr17:16757111-20219651 / R, D, P, S, M, L
Smith Magenis / RAI1 / Yes / Level 2 / chr17:17584787-17714767 / R, D, P, S, M, L
Sotos / NSD1 / Yes / Level 2 / chr5:176560080-176727214 / R, D, P
SOX2 related eye disorders / SOX2 / Yes / Level 2 / chr3:181429722-181432224 / R, D, P, S, M
Steroid sulfatase deficiency; X-linked ichthyosis / Xp22.31 / Yes / Level 2 / chrX:7137470-7272682 / R, M
Stickler Syndrome Type 1 / COL2A1 / Yes / Level 2 / chr12:48366748-48398285 / R, D, P, S, M, L
Supravalvular aortic stenosis / ELN / Yes / Level 2 / chr7:73442427-73484237 / R, D, P, S
Thrombocytopenia Absent Radius Syndrome / 1q21.1 / Yes / Level 2 / chr1:145401253-145928123 / R, D, P, S, L
Townes-Brocks Syndrome / SALL1 / Yes / Level 2 / chr16:51169886-51185183 / R, D, P, S
Treacher Collins Syndrome / TCOF1 / Yes / Level 2 / chr5:149737202-149779871 / R, D, P
Tuberous Sclerosis Complex / TSC2 / Yes / Level 2 / chr16:2097990-2138713 / R, D, P, S, M, O
Tuberous Sclerosis Complex / TSC1 / Yes / Level 2 / chr9:135766735-135820020 / R, D, P, S, M, O
Von-Hippel Lindau / VHL / Yes / Level 2 / chr3:10183319-10193762 / R, D, P, S, L
Waardenburg Type 1 / PAX3 / Yes / Level 2 / chr2:223064606-223163715 / R, D, P, M
WAGR Syndrome / 11p13 deletion / Yes / Level 2 / chr11:31803509-32510988 / R, D, P, S, L
Wilms Tumor / WT1 / Yes / Level 2 / chr11:32409325-32457087 / R, D, P, S
Wolf-Hirschhorn Syndrome / 4p16.3 / Yes / Level 2 / chr4:72448-2327204 / R, D, P, M
X-linked Adrenoleukodystrophy / ABCD1 / Yes / Level 2 / chrX:152990323-153010216 / R, D, P, S, M
X-linked Agammaglobulinemia / BTK / Yes / Level 2 / chrX:100604435-100641212 / R, D, S, M, O
X-linked Lymphoproliferative Syndrome / SH2D1A / Yes / Level 2 / chrX:123480132-123507010 / R, D, P, S, M
X-linked Lymphoproliferative Syndrome / XIAP / Yes / Level 2 / chrX:122994048-123047822 / R, D, P, S, M
X-linked periventricular heterotopia / FLNA / Yes / Level 2 / chrX:153576900-153603006 / R, D, P, S
2p16.1p15 Deletion Syndrome / 2p16.1p15 / Yes / Level 3 / chr2:57741796-61738334 / R, D, P
3q29 Deletion Syndrome / 3q29 / Yes / Level 3 / chr3:195756054-197344665 / R, D, P
7q21.2q21.3 Deletion Syndrome / 7q21.2q21.3 / Yes / Level 3 / chr7:95533860-96779486 / R, D, P
8p23.1 Deletion Syndrome / 8p23.1 / Yes / Level 3 / chr8:8119295-11765719 / R, D, P
10q23 Deletion Syndrome / 10q22q23 / Yes / Level 3 / chr10:81561778 -89310020 / R, D, P, S
16p13.11 Microdeletion Syndrome / 16p13.11 / Yes / Level 3 / chr16:15504454-16292268 / R, D, P
Autism Spectrum Disorders / SHANK3 / Yes / Level 3 / chr22:51113070-51171641 / R, D, S, L
Distal 22q11.2 Deletion Syndrome / 22q11.2 / Yes / Level 3 / chr22:22115848-23696229 / R, D, P
Maturity-Onset Diabetes of the Young, Type 5; MODY5 / HNF1B / Yes / Level 3 / chr17:36,046,433 - 36,105,095 / R, D, P, S
Oculo-facial-cardio-dental Syndrome / BCOR / Yes / Level 3 / chrX:39910499-40036582 / R, D, P
Renal Cysts and Diabetes Syndrome / 17q12 / Yes / Level 3 / chr17:34856056-36248918 / R, D, P, S
Resistance to Insulin-like Growth Factor I / 15q26 / Yes / Level 3 / chr15:99357970-102521392 / R, D, P, M
12q14 Microdeletion Syndrome / 12q14 / Yes / Level 4 / chr12:65071919-68645525 / R, D, P
14q11q22 Deletion Syndrome / 14q11.2 / Yes / Level 4 / chr14:21827160 -21862160 / R, D
Allan-Herndon-Dudley Syndrome / SLC16A2 / Yes / Level 4 / chrX:73641085-73753752 / R, D, P, M
Choroideremia / CHM / Yes / Level 4 / chrX:85116185-85302566 / R, D, P, S, M, L
Creatine Transporter Deficiency / SLC6A8 / Yes / Level 4 / chrX:152953752-152962048 / R, D, M
Hypohidrotic Ectodermal Dysplasia / EDA / Yes / Level 4 / chrX:68835911-69259322 / R, P, L
Joubert Syndrome (JBTS10) / OFD1 / Yes / Level 4 / chrX:13752832-13787480 / R, D, P, S, M
Langer Giedion Syndrome/TRPS2 / 8q24.1 / Yes / Level 4 / chr8:117,700,000 - 127,300,000 / R, D, P, S
Microphthalmia with linear skin defects (MLS) / HCCS / Yes / Level 4 / chrX:11129406-11141206 / R, D, P
Opitz G/BBB Syndrome / MID1 / Yes / Level 4 / chrX:10413350-10851809 / R, D, P
Simpson-Golabi-Behmel, Type 2 / OFD1 / Yes / Level 4 / chrX:13752832-13787480 / R, D, S
X-linked centronuclear myopathy / MTM1 / Yes / Level 4 / chrX:149737047-149841616 / R, D, S
1q41q42 Deletion Syndrome / 1q41q42 / Yes / Level 4 / chr1:214,500,000 - 236,600,000 / R, D
2q32q33 Deletion Syndrome / 2q32.2q33 / No / Level 4 / chr2:183,000,000 - 209,000,000 / None
Autism susceptibility / NLGN3 / No / Level 4 / chrX:70364681-70391051 / None
Early Infantile Epileptic Encephalopathy / ARHGEF9 / No / Level 4 / chrX:62854848-63005426 / None
L1 Syndrome / L1CAM / Yes / Level 4 / chrX:153126971-153141399 / R, D
Nonsyndromic hearing loss / PRPS1 / Yes / Level 4 / chrX:106871654-106894256 / R, D
X-linked mental retardation; Autism / NLGN4X / No / Level 4 / chrX:5808083-6146706 / None
Phenotype / Associated Gene/Genomic Region / Clinical Management Issues? / Level of Evidence / Coordinates (GRC 37/hg19) / Management Implications
Phenotypes associated with triplosensitivity mechanism
46,XY Complete Gonadal Dysgenesis/ Disorder of Sex Development / NR0B1 / Yes / Level 1 / chrX:30322539-30327495 / R, D, P, S, M, L
16p11.2 Duplication Syndrome / 16p11.2 / Yes / Level 2 / chr16:29649996-30199855 / R, D
3q29 Duplication Syndrome / 3q29 / Yes / Level 2 / chr3:195672229-197497869 / R, D, P, S
Charcot Marie Tooth 1a / 17p12 / Yes / Level 2 / chr17:14097914-15422955 / R, S, M
Charcot Marie Tooth, Type 1a / PMP22 / Yes / Level 2 / chr17:15133096-15168644 / R, S, M
MECP2 Duplication Syndrome / MECP2 / Yes / Level 2 / chrX:153287264-153363188 / R, D, S, M
Pelizaeus-Merzbacher Disease / PLP1 / Yes / Level 2 / chrX:103031439-103047548 / R, D
7q11.23 Duplication Syndrome / 7q11.23 / Yes / Level 3 / chr7:72744454-74142513 / R, D
15q26 Overgrowth Syndrome / 15q26 / Yes / Level 3 / chr15:99192760-99507759 / R, D, P
16p13.11 Duplication Syndrome / 16p13.11 / Yes / Level 3 / chr16:15504454-16284248 / D
17q12 Duplication Syndrome / 17q12 / Yes / Level 3 / chr17:34856056-36248918 / R, D
Cat-Eye Syndrome* / 22q11 (multiplication; copy number is 4) / Yes / Level 3 / chr22:17392953-18591860 / R, D, P, M
Potocki-Lupski Syndrome / 17p11.2 / Yes / Level 3 / chr17:16757111-20219651 / R, D, S
1q21.1 Duplication Syndrome / 1q21.1 / No / Level 4 / chr1:146577486-147394506 / None
15q11q13 Duplication Syndrome / 15q11q13 / Yes / Level 4 / chr15:23217513-28557186 / D
22q11.2 Duplication Syndrome / 22q11.2 / No / Level 4 / chr22:18661725-21561514 / None

Supplemental Figure

Figure 1: Sample Flow Diagram

1