Demographic and clinical characteristics of patients with TBK1 variants
| Variant | Sex | Age of onset (years) | Family history | Disease duration (months)* | ALSFRS-R progression rate † | Site of onset | Phenotype16 | Cognitive impairment25 |
| p.Leu59Phefs*16‡ | F | 36 | sALS | 52 § | 0.92 | Spinal | Classic | No |
| c.358+5G>A‡ | M | 62 | sALS | 17 | 0.7 | Spinal | PLMN | No |
| p.Asp118Asn¶ | M | 81 | sALS | 35 † | 0.6 | Spinal | PLMN | Yes (ALS-ECI) |
| p.Lys291Glu¶ | M | 74 | sALS / Δ | 33 | 0.57 | Spinal | Flail arm** | Yes (ALS-NECI) |
| p.Arg357Gln¶ | F | 36 | sALS | 20 | 1.2 | Spinal | Classic | No |
| p.Ile397Thr‡‡ | M | 65 | sALS / ϕ | 60 | 0.45 | Spinal | Pyramidal | Yes (ALS-ECI) |
| c.1644–5_1644-2delAATA‡‡ | M | 43 | sALS | 26 | 2.9 | Spinal | Pyramidal | No |
*Disease duration: time from disease onset to latest visit or death.
†Progression rate = (48-ALSFRS-R score)/disease duration.
‡Loss of function.
§Death.
¶Potentially pathogenic functional missense mutation.
**Hispanic ethnicity.
††Biological and pathogenetic relevance not clear by in vitro functional studies.
‡‡Not demonstrated as pathogenic.
ALSFRS-R, ALS Functional Rating Scale-revised; ALS-ECI, ALS with executive cognitive impairment; ALS-NECI, ALS with non-executive cognitive impairment; PLMN, pure lower motor neuron disease; sALS, sporadic amyotrophic lateral sclerosis; TBK1, TANK-binding kinase 1.
Δ: a brother and a sister deceased approximately at the age of 75 years reported to be affected by unclassified dementia. Φ: mother deceased at the age of 90 years reported to be affected by unclassified dementia.