Table 1.
TBK1 variants identified in Italian ALS cases
| Genomic coordinate (GRCh38) |
Variant (cDNA) | Protein change | Protein domain | dbSNP/ novel | EVS frequency | ExAC frequency |
SIFT score | Poly Phen2 Score |
Mutation Taster, p-value |
| g.64460277dupT | c.176dupT | p.Leu59Phefs*16 | KD | Novel | n.p. | n.p. | – | – | 1 (DC) |
| g.64464468+5G>A | c.358+5G>A | p.(?) | – | Novel | n.p. | n.p. | – | – | – |
| g.64464457G>A | c.352G>A | p.Asp118Asn | KD | rs200879808 | n.p. | 0.000008262 | 1.0 (T) | 0.939 (P) | 1 (DC) |
| g.64481900A>G | c.871A>G | p.Lys291Glu19 20 | KD | rs34774243 | 0.000233 | 0.0001733 | 0.03 (DE) | 0.997 (D) | 1 (DC) |
| g.64484380G>A | c.1070G>A | p.Arg357Gln8 | ULD | rs758357594 | n.p. | 0.000008333 | 0.28 (T) | 0.105 (B) | 1 (DC) |
| g.64484499T>C | c.1190T>C | p.Ile397Thr | ULD-CCD1 | rs755069538 | n.p. | 0.0001453 | 0.31 (T) | 0.039 (B) | 0.999 (DC) |
| g.64495694_64495697delAATA | c.1644–5_1644-2delAATA | p.(?) | – | rs755646937 | 0.005034 | 0.00009207 | – | – | – |
ALS, amyotrophic lateral sclerosis; B, benign; dbSNP, single nucleotide polymorphism database; D, probably damaging; cDNA, complementary DNA; DC, disease causing; DE, deleterious; EVS, Exome Variant Server; ExAC, Exome Aggregation Consortium; KD, kinase domain; n.p., not present; P, possibly damaging; T, tolerated; TBK1, TANK-binding kinase 1; ULD, ubiquitin-like domain; ULD-CCD1, region between ULD and coiled-coil domain 1.