Table 1 Analysed mutations in PSEN2, their location and associated AAOs
PSEN2 mutation | Position in PSEN2 | Mean AAO (range) | # Cases | Classification | |
|---|---|---|---|---|---|
1 | A85V | N-term | 61.5 (55.0–71.0) | 4 | Not classified |
2 | T122P | Loop 1 | 47.3 (46.0–50.0) | 3 | Likely pathogenic |
3 | P123L | Loop 1 | 57.0 | 1 | Not classified |
4 | E126K | Loop 1 | 53.5 (48.0–59.0) | 2 | Not classified |
5 | S130L | Loop 1 | 65.2 (51.0–81.0) | 9 | Uncertain significance |
6 | N141D | TMD 2 | 59.0 | 1 | Not classified |
7 | N141I | TMD 2 | 56.6 (40.0–76.0) | 87/101 (*) | Pathogenic |
8 | N141S | TMD 2 | 52.0 | 1 | Not classified |
9 | N141Y | TMD 2 | 46.0 (43.0–49.0) | 2 | Likely pathogenic |
10 | I149T | TMD 2 | 63.0 | 1 | Not classified |
11 | K161R | Loop 2 | 65.0 | 1 | Not classified |
12 | H169N | Loop 2 | 62.5 (56.0–68.0) | 4 | Uncertain significance |
13 | S175C | TMD 3 | 62.0 (60.0–65.0) | 3 | Not classified |
14 | S175F | TMD 3 | 53.0 (49.0–58.0) | 3 | Not classified |
15 | G212V | TMD 4 | 61.5 (60.0–65.0) | 4 | Not classified |
16 | I235F | TMD5 | 57.0 | 1 | Not classified |
17 | L238F | TMD 5 | 60.0 (49.0–74.0) | 4 | Uncertain significance |
18 | M239I | TMD 5 | 50.1 (30.0–58.0) | 16/20 (*) | Pathogenic |
19 | M239V | TMD 5 | 57.2 (45.0–83.0) | 28/44 (*) | Pathogenic |
20 | M239T | TMD 5 | 52.0 (47.0–59.0) | 3 | Pathogenic |
21 | R284G | Loop 6 | 57.5 (57.0–58.0) | 2 | Likely pathogenic |
22 | M298T | Loop 6 | 57.2 (56.0–59.0) | 5 | Likely pathogenic |
23 | A379D | Loop 7 | 55.0 | 1 | Not classified |
24 | P69A | N-term | 74.0 | 1 | Benign |
25 | R71W | N-term | 63.4 (55.0–75.0) | 9/18 (*) | Benign |
26 | V214L | TMD 4 | 57.2 (42.0–69.0) | 11/13 (*) | Benign |
27 | P334A | Loop 6 | Not reported | 1 | Benign |
28 | T421M | TMD 9 | 55.0 | 1 | Benign |