Mutations Position Table
APP I716 Mutations
| Mutation | Pathogenicity | DNA Change | Expected RNA | Protein Consequence | Coding/Non-Coding | Genomic Region | Neuropathology | Biological Effect | Primary Papers |
|---|---|---|---|---|---|---|---|---|
| I716F (Iberian) |
AD : Pathogenic | Substitution | Substitution | Missense | Coding | Exon 17 | Extensive mixed neuropathology, including neurofibrillary changes, amyloid deposits, and Lewy bodies. |
Increased Aβ42/Aβ40 ratio; decreased Aβ40 and AICD; increased Aβ1-38, Aβ1-39, Aβ1-42 and APP C-terminal fragments. Also, stalled γ-secretase-substrate complex tied to synaptic loss. |
Guerreiro et al., 2010 |
| I716V (Florida) |
AD : Not Classified | Substitution | Substitution | Missense | Coding | Exon 17 | Diffuse cortical atrophy, most prominant in the left anterior temporal lobe. |
Increased Aβ42(43)/Aβ40 ratio; increased Aβ42(43) and membrane-anchored Aβ48. Decreased Aβ48 → Aβ45 → Aβ42 → Aβ38 pathway. |
Eckman et al., 1997 |
| I716T |
AD : Not Classified | Substitution | Substitution | Missense | Coding | Exon 17 | Unknown. |
Increased Aβ42/Aβ40 and Aβ38/Aβ42 ratios and increased levels of longer Aβ peptides, including membrane-anchored Aβ49. Decreased total Aβ and AICD. Decreased ε-cleavage and shifted towards the Aβ48 → Aβ45 → Aβ42 → Aβ38 pathway. Stalled the γ-secretase-substrate complex in the membrane. |
Terreni et al., 2002 |
| I716M |
AD : Not Classified | Substitution | Substitution | Missense | Coding | Exon 17 | Unknown; MRI showed mild bilateral hippocampal atrophy. |
Unknown; predicted damaging in silico (PHRED-scaled CADD score > 20). |
Blauwendraat et al., 2016 |
These are all rare mutations, with only one family reported for each one to date. The amino acid change associated with these mutations occurs outside the Aβ sequence.
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