Table. 2 Phenotypic terms associated with PTV and missense variants (n = 409).

From: Computational analysis of 10,860 phenotypic annotations in individuals with SCN2A-related disorders

HPO term HPO code P value Odds ratio (95% CI) Frequency
PTV
 Behavioral abnormality HP:0000708 4.07×10-14 8.61 (4.57–17.01) 0.76
 Autism HP:0000717 1.06×10-13 8.16 (4.49–15.13) 0.63
 Autistic behavior HP:0000729 2.31×10-13 7.76 (4.26–14.50) 0.68
 Stereotypy HP:0000733 1.30×10-5 5.49 (2.45–12.22) 0.24
 Sleep disturbance HP:0002360 1.43×10-5 7.04 (2.76–18.32) 0.19
 Childhood onset HP:0011463 0.0004 3.57 (1.71–7.29) 0.25
 Delayed speech and language development HP:0000750 0.0005 3.72 (1.70–7.96) 0.22
 Intellectual disability, moderate HP:0002342 0.0013 3.83 (1.59–8.94) 0.18
 Neurodevelopmental abnormality HP:0012759 0.0023 2.58 (1.35–5.24) 0.79
 Short attention span HP:0000736 0.0047 3.83 (1.38–10.20) 0.13
 Hyperactivity HP:0000752 0.0047 3.83 (1.38–10.20) 0.13
 Attention deficit–hyperactivity disorder HP:0007018 0.0047 3.83 (1.38–10.20) 0.13
 Involuntary movements HP:0004305 0.01 2.65 (1.30–5.25) 0.25
Missense
 Neonatal onset HP:0003623 4.69×10-14 Inf (11.88–Inf) 0.40
 Seizures HP:0001250 3.71×10-13 8.91 (4.77–16.83) 0.89
 Epileptic spasms HP:0011097 1.44×10-6 Inf (4.39–Inf) 0.20
 Infantile spasms HP:0012469 2.62×10-6 Inf (4.15–Inf) 0.19
 Infantile onset HP:0003593 3.77×10-6 11.44 (2.93–98.45) 0.26
 Interictal epileptiform activity HP:0011182 8.29×10-6 3.71 (1.97–7.38) 0.51
 Focal-onset seizure HP:0007359 1.61×10-5 4.08 (1.98–9.26) 0.41
 Interictal EEG abnormality HP:0025373 2.85×10-5 3.42 (1.83–6.68) 0.51
 Abnormal nervous system electrophysiology HP:0001311 6.00×10-5 3.09 (1.70–5.80) 0.55
 EEG abnormality HP:0002353 6.00×10-5 3.09 (1.70–5.80) 0.55
 Abnormality of CNS electrophysiology HP:0030178 6.00×10-5 3.09 (1.70–5.80) 0.55
 Hypsarrhythmia HP:0002521 0.0001 Inf (2.88–Inf) 0.14
 EEG with burst suppression HP:0010851 0.0002 13.69 (2.27–558.40) 0.17
 Generalized-onset seizure HP:0002197 0.0005 2.77 (1.50–5.34) 0.48
 EEG with focal epileptiform discharges HP:0011185 0.0008 3.20 (1.50–7.61) 0.33
 EEG with generalized epileptiform discharges HP:0011198 0.0014 3.02 (1.46–6.88) 0.34
 Multifocal epileptiform discharges HP:0010841 0.0019 4.27 (1.51–16.70) 0.21
 Encephalopathy HP:0001298 0.0030 2.59 (1.31–5.53) 0.36
 Generalized tonic seizures HP:0010818 0.0030 4.20 (1.48–16.41) 0.21
 Epileptic encephalopathy HP:0200134 0.0065 2.50 (1.26–5.32) 0.35
 Focal tonic seizures HP:0011167 0.0077 5.39 (1.35–46.94) 0.14
 Abnormality of the cerebrum HP:0002060 0.01 2.84 (1.23–7.65) 0.25
  1. All significantly associated terms that remained significant after correction for multiple testing.
  2. CI confidence interval, CNS central nervous system, EEG electroencephalogram, HPO Human Phenotype Ontology, PTV protein-truncating variants.