Table 2.
TBK1 Predicted LoF Mutations in the European Study Population
| FTD | FTD‐ALS | ALS | |||
|---|---|---|---|---|---|
| cDNA | Predicted protein | n = 1,873 | n = 111 | n = 554 | Cohorts of the European study population |
| Protein‐truncating mutations leading to loss of transcript | |||||
| c.4C>T | p.Gln*2 | 1 | Belgian discovery cohort | ||
| c.86delA | p.Lys29Argfs*15 | 1 | European replication cohort | ||
| c.288delT | p.Val97Phefs*2 | 1 | European replication cohort | ||
| c.349C>T | p.Arg117* | 1 | European replication cohort | ||
| c.379C>T | p.Arg127* | 1 | European replication cohort | ||
| c.992+1G>T | p.Gly272_Thr331del | 1 | Belgian discovery cohort | ||
| c.1192delT | p.Ser398Profs*11 | 1 | Belgian discovery cohort | ||
| c.1335G>A | p.Trp445* | 1 | European replication cohort | ||
| c.1340+1G>A | p.Ala417* | 1 | European replication cohort | ||
| c.1385_1388delCAGA | p.Thr462Lysfs*3 | 1 | European replication cohort | ||
| c.1551_1552insTT | p.Ser518Leufs*32 | 1 | Belgian discovery cohort | ||
| In‐frame deletions leading to loss‐of‐protein or protein function | |||||
| c.235_237delACA | p.Thr79del | 1 | European replication cohort | ||
| c.499_501delGAT | p.Asp167del | 1 | Belgian discovery cohort | ||
| c.1927_1929delGAA | p.Glu643del | 3 | 1 | 2 | Belgian discovery cohort |
| Predicted in‐frame deletions with unknown effect | |||||
| c.228+1G>A | p.Lys30_Glu76del | 1 | European replication cohort | ||
| c.992+4_992+7delAGTA | p.Gly272_Thr331del | 1 | European replication cohort | ||
All listed mutations were absent from 2,183 screened control individuals and dbSNP build 138. The respective cohorts of the European study population in which mutations were identified are indicated in the last column. Mutations and carriers identified in the Belgian discovery cohort were previously published by our group [Gijselinck et al., 2015; Van Mossevelde et al., 2015]. Novel mutations and carriers reported in this study are part of the European replication cohort. cDNA numbering was according to the reference sequence NM_013254.3. In addition, for intronic variants, the genomic reference sequence NC_000012.12 was used. Nucleotide positions refer to cDNA sequence and nucleotide numbering uses +1 as the A of the ATG translation initiation codon in the reference sequence, with the initiation codon as codon 1. Protein numbering according to reference sequence NP_037386.1.