Table 2.
Phenotypic features nominally associated with variant groups
| Phenotypic feature (HPO code)a | Odds ratio (95% CI) | Group frequency |
|---|---|---|
| Association with protein truncating variants and deletions (PTV/del, n = 261)b in at least 20 individualsc | ||
| Abnormality of coordination (HP:0011443) | 1.86 (1.22–2.85) | 0.32 |
| Ataxia (HP:0001251) | 1.84 (1.20–2.84) | 0.30 |
| Abnormality of muscle physiology (HP:0011804) | 1.59 (1.11–2.29) | 0.56 |
| Abnormal muscle tone (HP:0003808) | 1.57 (1.09–2.26) | 0.54 |
| Muscular hypotonia (HP:0001252) | 1.59 (1.10–2.30) | 0.46 |
| Epileptic spasms (HP:0011097) | 1.57 (1.09–2.27) | 0.48 |
| Infantile spasms (HP:0012469) | 1.59 (1.08–2.35) | 0.38 |
| Neonatal onset (HP:0003623) | 1.61 (1.06–2.46) | 0.30 |
| Developmental regression (HP:0002376) | 0.52 (0.28–0.96) | 0.08 |
| Association with three most frequent recurrent variant hotspots in at least five individuals | ||
| p.Arg406Cys/His (n = 40) | ||
| Bruxism (HP:0003763) | 6.57 (2.29–17.4) | 0.20 |
| EEG with generalized epileptiform discharges (HP:0011198) | 2.82 (1.38–5.99) | 0.65 |
| Hypertonia (HP:0001276) | 2.95 (1.36–6.18) | 0.35 |
| Spastic tetraplegia (HP:0002510) | 4.92 (1.49–14.2) | 0.15 |
| Upper motor neuron dysfunction (HP:0002493) | 2.72 (1.28–5.63) | 0.38 |
| Inability to walk (HP:0002540) | 2.54 (1.15–5.05) | 0.38 |
| Spasticity (HP:0001257) | 2.77 (1.14–6.23) | 0.25 |
| EEG with burst suppression (HP:0010851) | 2.55 (1.13–5.46) | 0.30 |
| Dystonia (HP:0001332) | 2.95 (1.02–5.46) | 0.18 |
| p.Arg292Cys/His/Leu/Pro (n = 30) | ||
| Focal impaired awareness seizure (HP:0002384) | 2.94 (1.18–6.91) | 0.33 |
| Abnormal axial skeleton morphology (HP:0009121) | 2.63 (0.97–6.49) | 0.27 |
| p.Arg551Cys/Gly/His/Leu (n = 24) | ||
| Generalized-onset seizure (HP:0002197) | 2.81 (1.11–7.72) | 0.67 |
| Developmental regression (HP:0002376) | 3.06 (0.95–8.52) | 0.25 |
| Epileptic spasms (HP:0011097) | 0.35 (0.11–0.99) | 0.21 |
| EEG with abnormally slow frequencies (HP:0011203) | 2.53 (0.98–6.32) | 0.42 |
a
Positive and negative associations for each class by decreasing nominal significance are shown.
b
PTV/dels included splice sites, frameshifts and whole and partial gene deletions.
c
All nominal associations with PTV/del are shown in Supplementary Table 10.