Mutations Position Table

PSEN1 M233 Mutations

Mutation Clinical
Phenotype
Pathogenicity Neuropathology Biological Effect Genomic Position Genomic Region Mutation Type
Codon Change
Research
Models
Primary
Papers
M233I (G>C)
Alzheimer's Disease Alzheimer's Disease : Pathogenic

Neuropathology consistent with a diagnosis of AD, including amyloid plaques and tau-positive neurofibrillary tangles. No evidence of astrocytic gliosis, spongiosis, or prion disease.

Unknown. In silico algorithms predicted deleterious (CADD score > 20).

rs63751479
Coding
Exon 7
Point, Missense
ATG to ATC
0 Portet et al., 2003
M233I (G>A)
Alzheimer's Disease Alzheimer's Disease : Pathogenic

Unknown.

Unknown, but atomic structure indicates wild-type residue directly interacts with APP substrate.


Coding
Exon 7
Point, Missense
ATG to ATA
0 Wallon et al., 2012
M233L (A>C)
Alzheimer's Disease Alzheimer's Disease : Pathogenic

Unknown; imaging showed global cerebral atrophy.

In vitro, increased Aβ42 production, decreased Aβ40 production; increased Aβ42:Aβ40 ratio. In cells, increased Aβ42 and Aβ43, decreased total Aβ production, increased Aβ42:Aβ40 ratio. Disrupts endosomes via accumulation of APP β-CTF.

rs63751287
Coding
Exon 7
Point, Missense
ATG to CTG
0 Aldudo et al., 1999
M233L (A>T)
Alzheimer's Disease Frontotemporal Dementia : Not Classified

Unknown, but SPECT revealed hypoperfusion in posterior pariteal areas and a subsequent PET scan showed hypometabolism in prefrontal, parietal, and temporal cortices, in one case. MRI showed global cerebral atrophy.

Increased Aβ42 and decreased Aβ40 production, resulting in increased Aβ42/Aβ40 ratio in vitro. In cells, increased Aβ42/Aβ40 ratio, decreased total Aβ production and elevated levels of Aβ42 and Aβ43. Also, poromotes accumulation of APP β-CTFs which disrupt endosomes.

rs63751287
Coding
Exon 7
Point, Missense
ATG to TTG
0 Mendez and , 2006
M233T
Alzheimer's Disease Alzheimer's Disease : Pathogenic

Neuropathology consistent with AD in at least one case.

Increased Aβ42, Aβ48, and Aβ39; Decreased Aβ40, Aβ43, and Aβ46.

rs63751024
Coding
Exon 7
Point, Missense
ATG to ACG
1 Kwok et al., 1997
M233V
Alzheimer's Disease Alzheimer's Disease : Pathogenic

In one case: neurofibrillary tangles and amyloid plaques throughout the neocortex; occasional plaques in the spinal cord; Lewy bodies in the substantia nigra and cortex; moderate to severe amyloid angiopathy in leptomeningeal, cerebral, and cerebellar vessels. Widespread amyloid deposition in another patient as assessed by PET.

Increased Aβ42/Aβ40 ratio; increased Aβ42; decreased Aβ40. 

rs63751287
Coding
Exon 7
Point, Missense
ATG to GTG
0 Houlden et al., 2001

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