PSEN1 S170 Mutations

Mutation	Pathogenicity	DNA Change	Expected RNA \| Protein Consequence	Coding/Non-Coding	Genomic Region	Neuropathology	Biological Effect	Primary Papers
S170_ L171insY	AD : Not Classified	Insertion	Insertion \| Insertion	Coding	Exon 6	Unknown	Unknown	Koriath et al., 2018
S170F	AD : Pathogenic	Substitution	Substitution \| Missense	Coding	Exon 6	Variable: Some cases with typical AD pathology; Extensive Lewy bodies in the substantia nigra and throughout the brain have also been reported. One case had severe cerebellar pathology, including abundant amyloid deposition and loss of Purkinje cells.	Increased Aβ42/Aβ40 ratio in cells and in vitro, but effects on Aβ42 and Aβ40 levels varied between studies. Effects on calcium homeostasis, phospho-tau expression, autophagy, expression of mitochondrial fission and fusion proteins, cell viability, and trophic factor function have also been reported.	Snider et al., 2005
S170P	AD : Not Classified, Parkinsonism : Not Classified	Substitution	Substitution \| Missense	Coding	Exon 6	In AD case, typical AD tau pathology was reported. In parkinsonism case, MRI revealed hypointensity in the putamen, globus pallidus, and substantia nigra, as well as frontotemporal cortical atrophy. SPECT showed severe nigrostriatal dopaminergic deficit bilaterally, and 18F-FDG PET hypometabolism in striatal and posterior cingulate.	Unknown, but multiple in silico algorithms predicted a damaging effect.	Irwin et al., 2013; Carecchio et al., 2017

Mutation

Pathogenicity

DNA Change

Expected RNA | Protein Consequence

Coding/Non-Coding

Genomic Region

Neuropathology

Biological Effect

Primary
Papers

S170_ L171insY

AD : Not Classified

Insertion

Insertion | Insertion

Coding

Exon 6

Unknown

Koriath et al., 2018

S170F

AD : Pathogenic

Substitution

Substitution | Missense

Coding

Exon 6

Variable: Some cases with typical AD pathology; Extensive Lewy bodies in the substantia nigra and throughout the brain have also been reported. One case had severe cerebellar pathology, including abundant amyloid deposition and loss of Purkinje cells.

Increased Aβ42/Aβ40 ratio in cells and in vitro, but effects on Aβ42 and Aβ40 levels varied between studies. Effects on calcium homeostasis, phospho-tau expression, autophagy, expression of mitochondrial fission and fusion proteins, cell viability, and trophic factor function have also been reported.

Snider et al., 2005

S170P

AD : Not Classified, Parkinsonism : Not Classified

Substitution

Substitution | Missense

Coding

Exon 6

In AD case, typical AD tau pathology was reported. In parkinsonism case, MRI revealed hypointensity in the putamen, globus pallidus, and substantia nigra, as well as frontotemporal cortical atrophy. SPECT showed severe nigrostriatal dopaminergic deficit bilaterally, and 18F-FDG PET hypometabolism in striatal and posterior cingulate.

Unknown, but multiple in silico algorithms predicted a damaging effect.

Irwin et al., 2013;
Carecchio et al., 2017

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Mutations Position Table

PSEN1 S170 Mutations

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