Table 5.
Case reports of likely causal CNVs
| Subject | Subphenotype | 100 CHD Gene Region | Exon(s) | LOSS_GAIN | Cytoband | CNV Start (Build 36, hg18) | CNV Size, kb | Markers, n | Inheritance | Gene Names on CNV Segment (100 CHD Genes in boldface) |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | AS (valvar) | ACP6 BCL9 CHD1L FMO5 GJA5 PRKAB2 | all | Loss | 1q21.1 | 144643813 | 1654 | 684 | NBPF11 FAM108A3 PRKAB2 FMO5 CHD1L BCL9 ACP6 GJA5 GJA8 GPR89B NBPF11 | |
| 2 | AS (valvar) | CHD1L FMO5 PRKAB2 | all | Gain | 1q21.1 | 144943150 | 418 | 280 | PRKAB2 FMO5 CHD1L | |
| NSD1 | all | Gain | 5q35.2–5q35.3 | 175269980 | 1777 | 735 | THOC3 FAM153B C5orf25 KIAA1191 ARL10 HSPC111 HIGD2A CLTB FAF2 RNF44 PCDH24 GPRIN1 SNCB EIF4E1B TSPAN17 UNC5A HK3 UIMC1 ZNF346 FGFR4 NSD1 RAB24 PRELID1 MXD3 LMAN2 RGS14 SLC34A1 PFN3 F12 GRK6 PRR7 DBN1 PDLIM7 DOK3 DDX41 FLJ10404 TMED9 B4GALT7 | |||
| 3 | AS (valvar) | FOXC1 | all | Loss | 6p25.3–6p25.2 | 94649 | 2539 | 2130 | DUSP22 IRF4 EXOC2 HUS1B FOXQ1 FOXF2 FOXC1 GMDS C6orf195 MYLK4 | |
| 4 | ASD-SEC | MYH11 | all | Loss | 16p13.11–16p12.3 | 15186307 | 2903 | 1521 | MPV17L C16orf45 KIAA0430 NDE1 MYH11 C16orf63 ABCC1 ABCC6 NOMO3 LOC339047 XYLT1 | |
| 5 | ASD-SV | GATA4 | all | Loss | 8p23.1 | 11390744 | 304 | 213 | BLK GATA4 NEIL2 | |
| 6 | AVC (partial) | GATA4 SOX7 | all | Loss | 8p23.1 | 8055434 | 3844 | 3235 | PRAGMIN CLDN23 MFHAS1 THEX1 PPP1R3B TNKS MSRA UNQ9391 RP1L1 C8orf74 SOX7 PINX1 XKR6 MTMR9 AMAC1L2 FAM167A BLK GATA4 NEIL2 FDFT1 CTSB CTSB DEFB137 DEFB136 DEFB134 | |
| 7 | AVC (partial) | GDF1 | all | Gain | 19p13.11 | 18763592 | 378 | 163 | UPF1 GDF1 LASS1 COPE DDX49 HOMER3 SFRS14 ARMC6 SLC25A42 TMEM161A MEF2B | |
| 8 | AVC unbalanced + AVSD with ventricular imbalance | MID1 | 5′ UTR-i1 | Gain | Xp22.2 | 10714630 | 509 | 265 | MID1 HCCS ARHGAP6 AMELX | |
| 9 | AVSD with TOF | CRKL TBX1 | all | Gain | 22q11.21 | 17953160 | 1838 | 1106 | SEPT5 GP1BB TBX1 GNB1L C22orf29 TXNRD2 COMT ARVCF C22orf25 DGCR8 HTF9C RANBP1 ZDHHC8 RTN4R DGCR6L RIMBP3 ZNF74 SCARF2 KLHL22 MED15 PI4KA SERPIND1 SNAP29 CRKL AIFM3 LZTR1 THAP7 P2RX6 SLC7A4 | |
| 10 | CoA | ACP6 BCL9 CHD1L FMO5 GJA5 PRKAB2 | all | Gain | 1q21.1 | 144812585 | 1480 | 678 | PRKAB2 FMO5 CHD1L BCL9 ACP6 GJA5 GJA8 GPR89B GPR89C NBPF11 LOC728912 | |
| 11 | CoA | NOTCH1 | all | Loss | 9q34.3 | 138377108 | 229 | 105 | DNLZ CARD9 SNAPC4 SDCCAG3 PMPCA INPP5E SEC16A C9orf163 NO TCH1 | |
| 12 | DILV | HRAS | all | Gain | 11p15.5 | 354390 | 256 | 62 | B4GALNT4 PKP3 SIGIRR TMEM16J PTDSS2 RNH1 HRAS LRRC56 C11orf35 RASSF7 KIAA1542 IRF7 MUPCDH | |
| 13 | DORV | SEMA5A | i8-3′ UTR | Gain | 5p15.31–5p15.2 | 7119715 | 2152 | 1769 | ADCY2 C5orf49 FASTKD3 MTRR SEMA5A | |
| 14 | EBSTEIN'S | FKBP6 | 5′ UTR-i8 | Gain | 7q11.23 | 72073034 | 330 | 28 | TRIM74 STAG3L3 NSUN5 TRIM50 FKBP6 | |
| 15 | HLHS | EHMT1 | all | Gain | 9q34.3 | 139701521 | 264 | 142 | EHMT1 CACNA1B | |
| 16 | HLHS | FKBP6 | 5′ UTR-i8 | Gain | 7q11.23 | 72052197 | 348 | 34 | de novo | POM121 NSUN5C TRIM74 ST AG3L3 NSUN5 TRIM50 FKBP6 |
| 17 | HLHS | GATA4 | all | Gain | 8p23.1 | 11049252 | 1438 | 755 | unknown | XKR6 MTMR9 AMAC1L2 FAM167A BLK GATA4 NEIL2 FDFT1 CTSB DEFB137 DEFB136 DEFB134 DEFB130 ZNF705D DUB3 FAM86B1 DEFB130 |
| SOX7 | all | Gain | 8p23.1 | 8055434 | 2992 | 2584 | unknown | PRAGMIN CLDN23 MFHAS1 THEX1 PPP1R3B TNKS MSRA UNQ9391 RP1L1 C8orf74 SOX7 PINX1 XKR6 | ||
| 18 | HLHS | MYH11 | all | Gain | 16p13.11 | 14846829 | 1414 | 640 | inherited | NOMO1 NPIP PDXDC1 NTAN1 RRN3 MPV17L C16orf45 KIAA0430 NDE1 MYH11 C16orf63 ABCC1 ABCC6 NOMO3 |
| 19 | Other, Cardiac | CRKL TBX1 | all | Gain | 22q11.21 | 17161534 | 2634 | 1575 | DGCR6 PRODH DGCR2 DGCR14 TSSK2 GSC2 SLC25A1 CLTCL1 HIRA MRPL40 C22orf39 UFD1L CDC45L CLDN5 SEPT5 GP1BB TBX1 GNB1L C22orf29 TXNRD2 COMT ARVCF C22orf25 DGCR8 HTF9C RANBP1 ZDHHC8 RTN4R DGCR6L RIMBP3 ZNF74 SCARF2 KLHL22 MED15 PI4KA SERPIND1 SNAP29 CRKL AIFM3 LZTR1 THAP7 P2RX6 SLC7A4 | |
| 20 | PA, VSD | ACP6 BCL9 CHD1L FMO5 GJA5 PRKAB2 | all | Gain | 1q21.1 | 144812585 | 1480 | 678 | PRKAB2 FMO5 CHD1L BCL9 ACP6 GJA5 GJA8 GPR89B GPR89C NBPF11 LOC728912 | |
| 21 | Subaortic stenosis | CRKL | all | Gain | 22q11.21 | 19093207 | 699 | 626 | ZNF74 SCARF2 KLHL22 MED15 PI4KA SERPIND1 SNAP29 CRKL AIFM3 LZTR1 THAP7 P2RX6 SLC7A4 | |
| 22 | Subaortic stenosis | HRAS | all | Gain | 11p15.5 | 339238 | 271 | 63 | B4GALNT4 PKP3 SIGIRR TMEM16J PTDSS2 RNH1 HRAS LRRC56 C11orf35 RASSF7 KIAA1542 IRF7 MUPCDH | |
| 23 | DORV | FOXL2 NPHP3 | all | Gain | 3q22.1–3q26.1 | 131972967 | 32134 | 19750 | PIK3R4 ATP2C1 ATP2C1 ASTE1 NEK11 NUDT16 MRPL3 CPNE4 ACPP DNAJC13 ACAD11 CCRL1 UBA5 NPHP3 TMEM108 BFSP2 CDV3 TOPBP1 TF SRPRB RAB6B | |
| C3orf36 SLCO2A1 RYK AMOTL2 ANAPC13 CEP63 KY EPHB1 PPP2R3A MSL2L1 PCCB ST AG1 TMEM22 NCK1 IL20RB SOX14 CLDN18 DZIP1L A4GNT DBR1 ARMC8 TXNDC6 MRAS FAM62C CEP70 FAIM PIK3CB FOXL2 C3orf72 LOC389151 MRPS22 COPB2 RBP2 RBP1 NMNAT3 CLSTN2 TRIM42 SLC25A36 SPSB4 ACPL2 ZBTB38 RASA2 RNF7 GRK7 ATP1B3 TFDP2 GK5 XRN1 ATR PLS1 TRPC1 PCOLCE2 PAQR9 SR140 CHST2 SLC9A9 C3orf58 PLOD2 PLSCR4 PLSCR2 PLSCR1 PLSCR5 ZIC4 ZIC1 AGTR1 CPB1 CPA3 GYG1 HLTF HPS3 CP TM4SF18 TM4SF1 TM4SF4 WWTR1 COMMD2 RNF13 RNF13 PFN2 TSC22D2 SERP1 EIF2A SELT C3orf44 SIAH2 CLRN1 CLRN1 MED12L GPR171 P2RY14 GPR87 P2RY13 P2RY13 P2RY12 IGSF10 AADACL2 AADAC SUCNR1 MBNL1 TMEM14E P2RY1 RAP2B LOC152118 SGEF DHX36 GPR149 MME PLCH1 C3orf33 SLC33A1 GMPS KCNAB1 SSR3 TIPARP LEKR1 CCNL1 VEPH1 PTX3 C3orf55 SHOX2 RSRC1 MLF1 GFM1 LXN RARRES1 MFSD1 IQCJ SCHIP1 IL12A IFT80 SMC4 TRIM59 KPNA4 ARL14 PPM1L B3GALNT1 NMD3 C3orf57 OTOL1 SI SLITRK3 BCHE ZBBX SERPINI2 WDR49 PDCD10 SERPINI1 GOLIM4 EVI1 EVI1 MDS1 ARPM1 MYNN LRRC34 LRRIQ4 LRRC31 SAMD7 SEC62 GPR160 PHC3 PRKCI SKIL CLDN11 SLC7A14 RPL22L1 EIF5A2 SLC2A2 TNIK PLD1 FNDC3B GHSR TNFSF10 AADACL1 ECT2 SPATA16 NLGN1 NAALADL2 TBL1XR1 KCNMB2 ZMAT3 PIK3CA KCNMB3 ZNF639 MFN1 GNB4 ACTL6A MRPL47 NDUFB5 USP13 PEX5L TTC14 CCDC39 FXR1 DNAJC19 SOX2 ATP11B DCUN1D1 MCCC1 LAMP3 MCF2L2 B3GNT5 KLHL6 KLHL24 YEATS2 MAP6D1 PARL ABCC5 HTR3D HTR3C HTR3E | ||||||||||
| EIF2B5 DVL3 AP2M1 ABCF3 ALG3 ECE2 CAMK2N2 ECE2 PSMD2 EIF4G1 FAM131A CLCN2 POLR2H THPO CHRD EPHB3 MAGEF1 VPS8 C3orf70 EHHADH MAP3K13 TMEM41A LIPH SENP2 IGF2BP2 C3orf65 SFRS10 ETV5 DGKG CRYGS TBCCD1 DNAJB11 AHSG FETUB HRG KNG1 EIF4A2 RFC4 ADIPOQ ST6GAL1 RPL39L RTP1 MASP1 RTP4 SST RTP2 BCL6 LPP TPRG1 TP63 LEPREL1 SENP2 IGF2BP2 C3orf65 SFRS10 ETV5 DGKG CRYGS TBCCD1 DNAJB11 AHSG FETUB HRG KNG1 EIF4A2 RFC4 ADIPOQ ST6GAL1 RPL39L RTP1 MASP1 RTP4 SST RTP2 BCL6 LPP TPRG1 TP63 LEPREL1 | ||||||||||
| 24 | TOF | ACP6 BCL9 GJA5 | all | Gain | 1q21.1 | 145250193 | 1678 | 471 | BCL9 ACP6 GJA5 GJA8 GPR89B GPR89C NBPF11 LOC728912 PPIAL4 NBPF14 NBPF10 NBPF15 NBPF16 | |
| CHD1L FMO5 PRKAB2 | all | Gain | 1q21.1 | 144643813 | 600 | 223 | NBPF11 LOC728912 FAM108A3 PRKAB2 FMO5 CHD1L | |||
| 25 | TOF | CRKL | all | Loss | 22q11.21 | 18710744 | 1085 | 673 | RIMBP3 ZNF74 SCARF2 KLHL22 MED15 PI4KA SERPIND1 SNAP29 CRKL AIFM3 LZTR1 THAP7 P2RX6 SLC7A4 | |
| 26 | TOF | HOXA1 | all | Gain | 7p15.2–7p15.1 | 26113744 | 4718 | 3324 | NFE2L3 HNRNP A2B1 CBX3 SNX10 SKAP2 HOXA1 HOXA2 HOXA3 HOXA4 HOXA5 HOXA6 HOXA7 HOXA9 HOXA10 HOXA11 HOXA13 EVX1 HIBADH TAX1BP1 JAZF1 LOC402644 CREB5 KIAA0644 CPVL CHN2 PRR15 WIPF3 SCRN1 FKBP14 PLEKHA8 C7orf41 ZNRF2 NOD1 C7orf24 GARS CRHR2 INMT FLJ22374 | |
| TBX20 | all | Gain | 7p14.3–7p14.2 | 32897122 | 3321 | 2145 | KBTBD2 FKBP9 NT5C3 RP9 BBS9 BMPER NPSR1 DPY19L1 TBX20 HERPUD2 SEPT7 EEPD1 | |||
| 27 | TOF | MYH11 | all | Gain | 16p13.11 | 14805290 | 1455 | 642 | NOMO1 NPIP PDXDC1 NTAN1 RRN3 MPV17L C16orf45 KIAA0430 NDE1 MYH11 C16orf63 ABCC1 ABCC6 NOMO3 | |
| 28* | TOF | TERT | all | Loss | 5p15.33 | 80069 | 2948 | 1893 | PLEKHG4B LOC389257 CCDC127 SDHA PDCD6 LOC116349 EXOC3 SLC9A3 CEP72 TPPP ZDHHC11 BRD9 TRIP13 NKD2 SLC12A7 SLC6A19 SLC6A18 TERT CLPTM1L SLC6A3 LPCAT1 MRPL36 NDUFS6 IRX4 IRX2 C5orf38 | |
| 29 | TRI-AT | MAPK1 | all | Gain | 22q11.21–22q11.22 | 20264556 | 447 | 243 | UBE2L3 YDJC CCDC116 SDF2L1 PPIL2 YPEL1 MAPK1 PPM1F TOP3B | |
| 30 | TRI-AT | NSD1 | e24-3′ UTR | Gain | 5q35.3 | 176656286 | 330 | 133 | NSD1 RAB24 PRELID1 MXD3 LMAN2 RGS14 SLC34A1 PFN3 F12 GRK6 PRR7 DBN1 PDLIM7 DOK3 DDX41 FLJ10404 TMED9 B4GALT7 | |
| 31 | Truncus arteriosus | MAPK1 | all | Loss | 22q11.21–22q11.22 | 20055986 | 1237 | 863 | HIC2 RIMBP3B RIMBP3C UBE2L3 YDJC CCDC116 SDF2L1 PPIL2 YPEL1 MAPK1 PPM1F TOP3B VPREB1 ZNF280B ZNF280A PRAME | |
| GATA6 | all | Gain | 18q11.2 | 17749666 | 308 | 168 | GATA6 | |||
| 32 | Truncus arteriosus | SALL4 | all | Loss | 20q13.2 | 49428074 | 1839 | 1357 | NFATC2 ATP9A SALL4 ZFP64 TSHZ2 | |
| 33 | VSD (perimembranous) | CRKL | all | Gain | 22q11.21 | 19389671 | 406 | 451 | PI4KA SERPIND1 SNAP29 CRKL AIFM3 LZTR1 THAP7 P2RX6 SLC7A4 | |
| ACP6 BCL9 CHD1L FMO5 GJA5 PRKAB2 | all | Loss | 1q21.1 | 144723763 | 1574 | 683 | NBPF11 LOC728912 FAM108A3 PRKAB2 FMO5 CHD1L BCL9 ACP6 GJA5 GJA8 GPR89B GPR89C NBPF11 | |||
| 34 | VSD (perimembranous) | GATA4 SOX7 | all | Loss | 8p23.1 | 8027361 | 4456 | 3349 | PRAGMIN CLDN23 MFHAS1 THEX1 PPP1R3B TNKS MSRA UNQ9391 RP1L1 C8orf74 SOX7 PINX1 XKR6 MTMR9 AMAC1L2 FAM167A BLK GATA4 NEIL2 FDFT1 CTSB CTSB DEFB137 DEFB136 DEFB134 DEFB130 ZNF705D DUB3 FAM86B1 DEFB130 | |
| 35 | VSD (perimembranous) | GATA6 | all | Gain | 18q11.1–18q11.2 | 16795645 | 6118 | 3683 | ROCK1 ESCO1 SNRPD1 ABHD3 MIB1 GATA6 CTAGE1 RBBP8 CABLES1 C18orf45 RIOK3 C18orf8 NPC1 ANKRD29 LAMA3 TTC39C CABYR OSBPL1A IMPACT HRH4 ZNF521 SS18 PSMA8 TAF4B KCTD1 AQP4 AQP4 CHST9 |
*
Inconclusive TAQMAN results (see Subject 28). Boldface indicates confirmed genes. “Unknown” means one parental DNA was unavailable. “Other cardiac” phenotype (case 19) is double-chamber right ventricle (DCRV).