Table 4.
Top 5 genes with an overrepresentation of variants in mild or severe patients, per category of variants
| Type A variants (CADDa >20/ MAFb <0.01) | Type B variants (CADD >10/MAF <0.01) | Type C variants (all CADD/MAF <0.01) | Type D variants (all CADD/MAF <0.05) | Type E variants (all CADD/MAF <0.10) | |
|---|---|---|---|---|---|
| Genes with an excess of variants in mild patients (gene name [p‐value])c | SCN10A (.027) | SLC6A8 (.013) | EFHC1 (.002) | MOCS2 (.003) | MOCS2 (.003) |
| ACTL6B (.094) | SCN10A (.03) | SCN10A (.01) | KCNH1 (.008) | KCNH1 (.008) | |
| COL3A1 (.094) | RAI1 (.087) | SLC6A8 (.013) | EFHC1 (.01) | DRD4 (.009) | |
| DEPDC5 (.094) | ACTL6B (.094) | DSC2 (.027) | SLC6A8 (.013) | SLC6A8 (.013) | |
| KPNA7 (.094) | COL3A1 (.094) | RAI1 (.087) | MYT1 (.027) | CTSD (.026) | |
| Genes with an excess of variants in severe patients (gene name [p‐value]) | GPR98 (.049) | GPR98 (.201) | GPR98 (.193) | RYR2 (.025) | RYR2 (.013) |
| RYR2 (.419) | CUX1 (.314) | ANKRD11 (.3) | CUX1 (.049) | CUX1 (.049) | |
| ITPR1 (.564) | RYR2 (.417) | ANK2 (.314) | KCNB1 (.088) | KCNB1 (.088) | |
| SIK1 (.564) | CUX1 (.314) | ANK2 (.094) | AKAP9 (.094) | ||
| TSC1 (.564) | RYR2 (.417) | AKAP9 (.094) | ANK2 (.094) |
a
PHRED‐scaled CADD (combined annotation dependent depletion). A score of >20 represents the top 1% deleterious substitutions in the human genome.
b
Minor allele frequency; only variants with a frequency below this threshold in both the exomes and genomes in the gnomAD database are included.
c
p‐values are based on Fishers' exact test.