Table 2.
Information regarding the rare variants identified in the TOF patients
| Gene | Nucleotide change | Amino acid change | Patient ID | Diagnosis | Scores of SIFT/PolyPhen/MutationTaster | SIFT/PolyPhen/MutationTaster | ExAC/1 KG (frequency) | Patients (n = 106) | Internal database | ClinVar |
|---|---|---|---|---|---|---|---|---|---|---|
| JAG1 | c. 1511A>G | N504S | B151 | TOF/PFO | 0.04/0.07/0.1 | D/B/D | 0.00004/0 | 1 | 2 | Likely pathogenic |
| c. 3038A>T | H1013L | B393* | TOF | 0.02/0.601/1 | D/P/D | 0.0001/0 | 1 | 0 | ||
| c. 2906T>C | M969T | B294* | TOF | 0.042/0.001/1 | T/B/D | 0/0 | 1 | 0 | ||
| c. 806C>G | P269R | B431 | TOF/ASD | 0/1/1 | D/D/D | 0/0 | 1 | 0 | ||
| GATA4 | c. 1220C>A | P407Q | B445,B548* | TOF/PFO | 0.05/0.145/1 | D/B/D | 0.0006/0.0012 | 2 | 1 | Pathogenic |
| c. 1138G>A | V380 M | B445,B548* | TOF/PFO | 0.49/0.002/0.002 | T/B/N | 0.0063/0.0156 | 2 | 2 | ||
| GATA5 | c. 943T>A | S315T | B314 | TOF/PFO | 0.69/0.006/0 | T/B/N | 0/0 | 1 | 0 | |
| c. 274G>T | A92S | B294* | TOF | 0.83/0.097/0.001 | T/B/N | 0/0 | 1 | 0 | ||
| GATA6 | c. 331G>A | D111 N | B413 | TOF | 0.19/0.069/1 | T/B/D | 0/0 | 1 | 0 | |
| c. 972C>G | H324Q | B393* | TOF | 0.3/0.846/0.026 | T/P/N | 0/0 | 1 | 0 | ||
| ZFPM2 | c. 3442G>A | E1148 K | B430 | TOF/PFO | 0/0.985/1 | D/D/D | 0/0 | 1 | 0 | |
| c. 3014A>G | E1005G | B546 | TOF | 0.2/0.073/1 | T/B/D | 0.0001/0.0002 | 1 | 0 | ||
| TBX2 | c. 2139dupG | Frameshift | B326 | TOF/AVSD | ././. | ././. | 0/0 | 1 | 0 | |
| TBX5 | c. 409G>T | V137L | A1114 | TOF/PDA/PFO | 0.02/0.772/1 | D/P/D | 0/0 | 1 | 0 | |
| CITED2 | c.-1A>T | Splice | B303 | TOF/PAA | ././1 | ././D | 0/0 | 1 | 0 |
* More than one rare variant was found in one case
TOF Tetralogy of Fallot, ASD Atrial septum defect, ACSD Atrioventricular septum defect, LSVC Left superior vena cava, PDA Patent ductus arteriosus, PFO Patent foramen ovale, PAA pulmonary artery absent, SIFT, “D” meaning deleterious, score less than 0.05, “T” meaning tolerated, score greater than or equal to 0.05; PolyPhen2, “D” meaning likely damaging, 0.957 ≤ score ≤ 1, “P” meaning likely damaging, 0.453 ≤ score ≤ 0.956, “B” meaning benign, 0 ≤ score ≤ 0.452; MutationTaster, “A” represents as disease causing automatic meaning known deleterious reported in HGMD/ClinVar/dbSNP, “D” represents as disease causing meaning likely deleterious, “N” represents polymorphism or likely harmless, “P” represents polymorphism automatic meaning known harmless. ExAC, Exome Aggregation Consortium; 1 KG, 1000 genome; Internal database: n = 3215, whole- exome sequencing data from the molecular laboratory of the Children Hospital of Fudan University; “0” in frequency means didn’t find in the database