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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