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Table 2 Discovery genes ascertained via case-exclusive LOF sites with evidence for a role in LSLs

From: Whole exome sequencing in 342 congenital cardiac left sided lesion cases reveals extensive genetic heterogeneity and complex inheritance patterns

Gene Chr. LSL Clinical cohort Gene support LOF OP (%ile) pLI
LSL ID Mode CVM Non-CVM
ACVR1 2 LO1462 De novo 0 0 MGI, HE, TGFB 0.201 0.96
JARID2 6 LO0189 De novo 1 0 MGI, PITX2 0 0.99
KMT2D 12 LO0785 De novo 7 13 CVM 0 1
NF1 17 LO2000 De novo 1 4 CVM, MGI, HE 0.166 1
NR2F2 15 LO0260 De novo 0 0 CVM, MGI 0 0.91
PLRG1 4 LO0943 De novo 0 0 MGI 0 0.99
SMURF1 7 LO1765 De novo 1 0 TGFB 0 0.99
TBX20 7 LO0746 De novo 0 0 CVM, MGI, HE 0 0.34
ZEB2 2 LO0747 De novo 6 4 CVM, ZFIN 0 0.99
ARHGEF11 1 LO2218 Inherited 2 0 ZFIN 0.156 0.99
CCDC91 12 LO0222 Inherited 1 3 PITX2 0 3.2E-05
CDH2 18 LO1263 Inherited 2 2 MGI, HE, PITX2 0.077 1
E2F6 2 LO0970 Inherited 0 0 PITX2 0 0.55
FGF19 11 LO1957 Inherited 0 0 MGI 0 0.29
GJC1 17 LO0192 Inherited 0 0 MGI, ZFIN 0 0.94
GLRX3 10 LO0350 Inherited 0 0 MGI, HE 0 0.63
LATS2 13 LO0238 Inherited 2 4 MGI 0.119 0.87
LTBP1 2 LO2218 Inherited 1 2 MGI, TGFB 0 0.53
MNDA 1 LO0369 Inherited 0 0 CHD candidate 0.265 7.2E-11
PCDHGA2 5 LO0605 Inherited 0 4 HE 0 8.2E-07
PCSK6 15 LO1210 Inherited 2 3 MGI 0 0.01
RAC1 7 LO0938 Inherited 0 0 MGI, HE 0 0.57
DNAH5 5 LO1298 Recessive 6 30 CVM, MGI, HE, PCD 0.299 5.8E-37
OFD1 X LO1488 X-linked 1 3 CVM, MGI, ZFIN 0 0.98
BMP1 8 LO0605 Unknown 0 1 MGI 0 0.87
JMJD6 17 LO0295 Unknown 0 1 MGI 0 0.82
ROCK1 18 LO0453 Unknown 1 5 MGI, TGFB, PITX2 0 1
  1. Inheritance was determined by Sanger sequencing in cases and parents. The number of samples in the clinical laboratory cohort with any LOF alleles in these genes is also provided along with current CVM status. Unknown inheritance indicates only one parent was available for validation and did not carry the mutation
  2. Gene support symbols are defined as follows: CVM known role in human cardiovascular malformation, MGI overlapping phenotype in mouse, HE human heart expressed, PITX2 related to PITX2 transcription, ZFIN overlapping phenotype in zebrafish, TGFB transforming growth factor beta pathway
  3. LOF OP ratio percentile calculated from ARIC EA participants. Functional gene constraint values (pLI) from the Exome Aggregation Consortium (ExAC) Browser (cleaned_exac_r03_march16_z_pli_rec_null_data) are provided for reference