Table 3. Number of variants in each pathogenicity class observed in the present dataset.
The total number of variants in each variant pathogenicity class identified in each of the respective cohorts is shown as well as a percentage of the number of cases in each cohort for those of uncertain or at least possible pathogenicity. In 1052 AD patients, 15 novel DVs were identified; in 794 FTD patients, 24 novel DVs were identified, in prion patients one novel DV was identified, and in DemMot patients three novel DVs were identified. In 243 patient and control samples we could not be certain of age at onset, therefore the sum of Early and Late-Onset does not equal All Ages. A DV was identified in two healthy elderly control samples; one 67 year old male carried the PRNP Gln212Pro variant and one male 77 year old was found to carry a frameshift mutation in GRN (c.708+5_708+8delGTGA) affecting a splice-site. AAO for both PRNP and GRN ranges into old age.
| N Variants | Deleterious | Likely deleterious | Novel DVs | Possible | Uncertain | Likely benign | Benign | Risk Factor | Synonymous | Total N Cohort | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Early-Onset | AD | 38 (4.6%) | 19 (2.3%) | 12 (1.5%) | 34 (4.2%) | 70 (8.6%) | 39 (4.8%) | 545 (66.6%) | 147 (18%) | 1957 (239.2%) | 818 |
| FTD | 112 (23%) | 10 (2.1%) | 14 (2.9%) | 13 (2.7%) | 65 (13.3%) | 24 (4.9%) | 314 (64.5%) | 81 (16.6%) | 1364 (280.1%) | 487 | |
| Prion | 57 (35%) | 1 (0.6%) | 0 (0%) | 4 (2.5%) | 2 (1.2%) | 5 (3.1%) | 93 (57.1%) | 29 (17.8%) | 563 (345.4%) | 163 | |
| DemMot | 19 (4.3%) | 4 (0.9%) | 2 (0.4%) | 14 (3.1%) | 20 (4.5%) | 24 (5.4%) | 278 (62.2%) | 82 (18.3%) | 1221 (273.2%) | 447 | |
| Controls | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 47 (1175%) | 5 (125%) | 2 (50%) | 17 (425%) | 4 | |
| Total | 226 (11.8%) | 34 (1.8%) | 29 (1.5%) | 65 (3.4%) | 157 (8.2%) | 139 (7.2%) | 1234 (64.3%) | 341 (17.8%) | 5122 (266.9%) | 1919 | |
| Late-Onset | AD | 9 (4%) | 4 (1.8%) | 3 (1.3%) | 12 (5.3%) | 9 (4%) | 91 (40.3%) | 166 (73.5%) | 39 (17.3%) | 698 (308.8%) | 226 |
| FTD | 16 (9.9%) | 2 (1.2%) | 3 (1.9%) | 6 (3.7%) | 20 (12.3%) | 59 (36.4%) | 84 (51.9%) | 34 (21%) | 451 (278.4%) | 162 | |
| Prion | 5 (7.5%) | 1 (1.5%) | 0 (0%) | 2 (3%) | 1 (1.5%) | 17 (25.4%) | 29 (43.3%) | 21 (31.3%) | 204 (304.5%) | 67 | |
| DemMot | 2 (1.1%) | 1 (0.6%) | 0 (0%) | 8 (4.5%) | 6 (3.4%) | 85 (48.3%) | 100 (56.8%) | 17 (9.7%) | 471 (267.6%) | 176 | |
| Controls | 2 (0.4%) | 0 (0%) | 0 (0%) | 5 (1.1%) | 12 (2.7%) | 3 (0.7%) | 314 (70.1%) | 49 (10.9%) | 1415 (315.8%) | 448 | |
| Total | 34 (3.2%) | 8 (0.7%) | 6 (0.6%) | 33 (3.1%) | 48 (4.4%) | 254 (23.5%) | 690 (63.9%) | 160 (14.8%) | 3239 (300.2%) | 1079 | |
| All Ages | AD | 48 (4.6%) | 23 (2.2%) | 15 (1.4%) | 46 (4.4%) | 79 (7.5%) | 130 (12.4%) | 717 (68.2%) | 187 (17.8%) | 2676 (254.4%) | 1052 |
| FTD | 155 (19.5%) | 14 (1.8%) | 20 (2.5%) | 24 (3%) | 107 (13.5%) | 99 (12.5%) | 500 (63%) | 132 (16.6%) | 2262 (284.9%) | 794 | |
| Prion | 82 (27.4%) | 3 (1%) | 1 (0.3%) | 6 (2%) | 6 (2%) | 35 (11.7%) | 162 (54.2%) | 67 (22.4%) | 999 (334.1%) | 299 | |
| DemMot | 22 (3.4%) | 5 (0.8%) | 3 (0.5%) | 23 (3.6%) | 32 (5%) | 119 (18.6%) | 387 (60.6%) | 106 (16.6%) | 1750 (273.9%) | 639 | |
| Controls | 2 (0.4%) | 0 (0%) | 0 (0%) | 5 (1.1%) | 12 (2.6%) | 51 (11.2%) | 321 (70.2%) | 54 (11.8%) | 1447 (316.6%) | 457 | |
| Total (% of patients) | 309 (9.5%) | 45 (1.4%) | 39 (1.2%) | 104 (3.2%) | 236 (7.3%) | 435 (13.4%) | 2087 (64.4%) | 546 (16.8%) | 9134 (281.8%) | 3241 | |