Table 1 Identified variants of the PSEN1 gene in 8 EOFAD patients.
Patient No. | Exon | Nucleotide change | Amino acid change | Protein domain | APOE genotype | In silico analysis | rs number | GERP score | CADD score | gnomAD* (non-neuro cohort) | ALZFORUM Mutation Database† | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
PolyPhen-2 (Probabilistic score) | SIFT (Tolerance index) | |||||||||||
Pathogenic variants | ||||||||||||
1 | 5 | c.358 G > A | p.Glu120Lys | NA | ε2/ε3 | Probably damaging (1.000) | Not tolerable (0.00) | rs63750800 | 4.74 | 27.0 | NA | Pathogenic |
2 | 6 | c.509 C > T | p.Ser170Phe | 3rd TM | ε3/ε3 | Probably damaging (1.000) | Not tolerable (0.00) | rs63750577 | 4.57 | 25.5 | 0.000024 | Pathogenic |
Likely pathogenic variants | ||||||||||||
3 | 5 | c.356 C > T | p.Thr119Ile | NA | ε3/ε4 | Probably damaging (0.973) | Tolerable (0.11) | NA | 4.74 | 24.0 | NA | Pathogenic |
4 | 5 | c.476 A > G | p.Tyr159Cys | NA | ε3/ε4 | Probably damaging (1.000) | Not tolerable (0.00) | rs778630379 | 4.65 | 28.3 | 0.000005 | NA |
5 | 8 | c.845 T > C | p.Leu282Pro | NA | ε3/ε3 | Probably damaging (0.998) | Not tolerable (0.00) | NA | 5.70 | 28.5 | NA | NA |
6 | 8 | c.853 G > T | p.Ala285Ser | NA | ε3/ε3 | Probably damaging (1.000) | Tolerable (0.14) | NA | 5.82 | 25.9 | NA | NA |
Variants of unknown significance | ||||||||||||
7 | 11 | c.1165 T > C | p.Tyr389His | 7th TM | ε3/ε4 | Probably damaging (0.998) | Not tolerable (0.00) | NA | 4.54 | 26.9 | NA | NA |
8 | 11 | c.1166 A > C | p.Tyr389Ser | 7th TM | ε3/ε3 | Probably damaging (0.999) | Not tolerable (0.00) | NA | 4.53 | 26.8 | NA | NA |
