Mutations
APP
APP encodes amyloid precursor protein, a transmembrane protein which is cleaved to form amyloidogenic Aβ peptides. Mutations in APP are associated with familial forms of early onset Alzheimer's disease as well as with Cerebral Amyloid Angiopathy (CAA). Pathogenic mutations generally alter processing by secretases, leading in an overall increase in Aβ production and/or a change in the ratio of specific Aβ peptides.

Search Results
APP (73)
Mutation | Clinical Phenotype |
Pathogenicity | Neuropathology | Biological Effect | Genomic Position | Genomic Region | Mutation Type Codon Change |
Research Models |
Primary Papers |
---|---|---|---|---|---|---|---|---|---|
S198P |
Alzheimer's Disease | AD : Benign | Unknown. | The S198P mutation increased the production of Aβ in cultured cells and in a transgenic mouse model of amyloidosis. | rs145081708 |
Coding Exon 5 |
Point, Missense TCT to CCT |
0 | Zhang et al., 2021 |
A201V |
None, Parkinson's Disease Dementia | AD : Benign, PDD : Not Classified | Not applicable. | In cells, no effect on Aβ42, Aβ40, and Aβ42/Aβ40. | rs149995579 |
Coding Exon 5 |
Point, Missense GCG to GTG |
0 | Sassi et al., 2014 |
A235V |
Alzheimer's Disease | AD : Benign | Unknown. | Decreased aβ40 and Aβ42 without changing Aβ42/Aβ40 ratio in cells. | Coding Exon 6 |
Point, Missense GCT to GTT |
0 | Nicolas et al., 2015 | |
D243N |
Alzheimer's Disease | AD : Benign | Unknown. | No effect on Aβ42 or Aβ40 production in cells. | Coding Exon 6 |
Point, Missense GAT to AAT |
0 | Nicolas et al., 2015 | |
D244G |
Alzheimer's Disease | AD : Not Classified | Unknown. | Unknown, but predicted to be probably damaging by PolyPhen-2 and tolerated by SIFT. PHRED-scaled CADD score > 20. | rs1347585131 |
Coding Exon 6 |
Point, Missense GAT to GGT |
0 | Jiang et al., 2019 |
E246K |
Alzheimer's Disease | AD : Likely Benign | Unknown. | In cells, no significant effect on Aβ40 or Aβ42 production. | rs147485129 |
Coding Exon 6 |
Point, Missense GAG to AAG |
0 | Sala Frigerio et al., 2015 |
E296K |
Alzheimer's Disease | AD : Not Classified | Unknown. | Unknown, but in silico PHRED-CADD score >20, suggesting damaging effect. | Coding Exon 7 |
Point, Missense GAG to AAG |
0 | Nicolas et al., 2015 | |
T297M |
Alzheimer's Disease | AD : Uncertain Significance | Unknown. | Unknown, but predicted to be damaging by PolyPhen-2 and deleterious by SIFT (PHRED-scaled CADD score > 20). | rs557227002 |
Coding Exon 7 |
Point, Missense ACG to ATG |
0 | Jiang et al., 2019 |
P299L |
Alzheimer's Disease | AD : Not Classified | Unknown. | Unknown, but predicted to be damaging in silico (PHRED-scaled CADD score >20). | Coding Exon 7 |
Point, Missense CCG to CTG |
0 | Nicolas et al., 2015 | |
D332G |
Alzheimer's Disease | AD : Not Classified | Unknown, but MRI showed atrophy of the hippocampus and of the temporal and parietal lobes. | Unknown, but predicted to be damaging by PolyPhen-2 and tolerated by SIFT. | rs773998162 |
Coding Exon 7 |
Point, Missense GAC to GGC |
0 | Jiang et al., 2019 |
V340M |
Alzheimer's Disease | AD : Uncertain Significance | Unknown. | Unknown, but its PHRED-scaled CADD score was >20 suggesting a deleterious effect. | rs768499633 |
Coding Exon 7 |
GTG to ATG |
0 | Lee et al., 2014 |
E380K |
Alzheimer's Disease | AD : Uncertain Significance | Unknown, but imaging revealed brain atrophy. | Unknown, but predicted to be probably damaging by PolyPhen-2, damaging by SIFT, and neutral by PROVEAN. PHRED-scaled CADD score > 20. | rs755703063 |
Coding Exon 9 |
Point, Missense GAG to AAG |
0 | El Bitar et al., 2019 |
R468H |
None | AD : Benign | Not applicable. | In cells, neither Aβ40 nor Aβ42 production significantly affected. | Coding Exon 11 |
Point, Missense CGC to CAC |
0 | Schulte et al., 2015 | |
A479S |
None | AD : Benign | Not applicable. | In cells, no significant effect on Aβ40 or Aβ42 production. | rs143794560 |
Coding Exon 11 |
Point, Missense GCT to TCT |
0 | Sala Frigerio et al., 2015 |
R486W |
Alzheimer's Disease | AD : Not Classified | Unknown. | Unknown, but predicted to be probably damaging by in silico algorithms (PHRED-scaled CADD score > 20). | rs201085152 |
Coding Exon 11 |
Point, Missense CGG to TGG |
0 | Wang et al., 2019 |
K496Q |
Alzheimer's Disease | AD : Not Classified | One reported carrier of this variant had autopsy-confirmed AD. | In cells, slight increase in Aβ40, but Aβ42/Aβ40 ratio not significantly different from controls. | rs201384815 |
Coding Exon 12 |
Point, Missense AAG to CAG |
0 | Sassi et al., 2014 |
A500T |
None | AD : Not Classified | Not applicable. | In cells, Aβ40 and Aβ42 production was similar to wildtype APP. | rs201547994 |
Coding Exon 12 |
Point, Missense GCA to ACA |
0 | Schulte et al., 2015 |
Y538H |
Alzheimer's Disease | AD : Benign | Neuropathology consistent with AD, but not thought to be attributed to this variant. | Decreased Aβ42 and Aβ40 in cells, without altering Aβ42/Aβ40 ratio. | rs45537238 |
Coding Exon 13 |
Point, Missense TAT to CAT |
0 | Sassi et al., 2014 |
V562I |
None | AD : Not Classified | Not applicable. | In cells, Aβ40 secretion was slightly decreased with no change in Aβ42 secretion. Aβ42/Aβ40 was not significantly different from controls. | rs199586073 |
Coding Exon 13 |
Point, Missense GTT to ATT |
0 | Sassi et al., 2014 |
E599K |
Alzheimer's Disease, Parkinson's Disease | AD : Benign, PD : Not Classified | Not applicable. | In cells, reduced Aβ40 secretion, but did not significantly alter Aβ42 secretion nor the Aβ42/Aβ40 ratio. | rs140304729 |
Coding Exon 14 |
Point, Missense GAA to AAA |
0 | Sassi et al., 2014 |
T600M |
None | AD : Benign | Not applicable. | In cells, secreted less Aβ40, but Aβ42 secretion and the Aβ42/Aβ40 ratio were not significantly altered. | rs200088099 |
Coding Exon 14 |
Point, Missense ACG to ATG |
0 | Schulte et al., 2015 |
V604M |
Alzheimer's Disease, Progressive Nonfluent Aphasia | AD : Uncertain Significance | Unknown, but MRI showed atrophy of the frontoparietal cortex and hippocampus. | Unknown. Predicted in silico to be deleterious (PHRED-scaled CADD score >20). | rs199887707 |
Coding Exon 14 |
Point, Missense GTG to ATG |
0 | Van Giau et al., 2018 |
S614G |
Alzheimer's Disease | AD : Uncertain Significance | Unknown. | Increased Aβ42/Aβ40 ratio, with a decrease in Aβ40 and an increase in Aβ42 secretion in a cellular assay. | rs112263157 |
Coding Exon 14 |
Point, Missense AGC to GGC |
0 | Lee et al., 2014 |
P620A |
Alzheimer's Disease | AD : Not Classified | Unknown. | Increased Aβ42 and the Aβ42/Aβ40 ratio in cells. | Coding Exon 14 |
Point, Missense CCG to GCG |
0 | Nicolas et al., 2015 | |
P620L |
Alzheimer's Disease | AD : Uncertain Significance | One reported carrier of the variant had autopsy-confirmed AD. | Increased Aβ40 and Aβ42 secretion in cells, without significantly altering the Aβ42/Aβ40 ratio in cells. | Coding Exon 14 |
Point, Missense CCG to CTG |
0 | Sassi et al., 2014 | |
T663M |
Parkinson's Disease Dementia | PDD : Not Classified | Unknown. | Unknown, but in silico predicted to be deleterious (PHRED-scaled CADD score >20). | rs200260102 |
Coding Exon 16 |
Point, Missense ACG to ATG |
0 | Schulte et al., 2015 |
E665D |
None | AD : Benign | Not applicable. | Aβ42, Aβ40, and the Aβ42/Aβ40 ratio were not significantly different from those of cells expressing wildtype APP. | rs63750363 |
Coding Exon 16 |
Point, Missense GAG to GAC |
0 | Peacock et al., 1994 |
V669L (Seoul) |
Alzheimer's Disease | AD : Not Classified | Unknown, although MRI showed pronounced cerebral atrophy that included the hippocampus. | Unknown. Although results were mixed, an integrative in silico prediction tool predicted damaging effects (PHRED-scaled CADD score >20). | rs1259157720 |
Coding Exon 16 |
Point, Missense GTG to CTG |
0 | Bagyinszky et al., 2019 |
KM670/671NL |
Alzheimer's Disease | AD : Pathogenic | Generalized atrophy with sulcal widening and mild ventricular enlargement. | Increased total Aβ; unchanged Aβ42/Aβ40 ratio; increased production and secretion of Aβ42 and Aβ40. | rs63751263, rs63750445 |
Coding Exon 16 |
Point, Double AAG.ATG to AAT.CTG |
75 | Mullan et al., 1992 |
A673T (Icelandic) |
None | AD : Protective | This variant is associated with minimal amyloid deposition and is thought to protect against amyloid pathology. | Reduced production of amyloidogenic Aβ peptides by about 40 percent. The Aβ generated is less prone to aggregation. | rs63750847 |
Coding Exon 16 |
Point, Missense GCA to ACA |
1 | Peacock et al., 1993; Jonsson et al., 2012 |
A673V |
Alzheimer's Disease | AD : Not Classified | Definite AD by CERAD criteria, with extensive deposition of Aβ and tau pathology (Braak stage VI). Cerebral amyloid angiopathy. Deposits contained high levels of Aβ40 and were noted to be unusually large, with few preamyloid deposits. Localization was frequently perivascular. | In vitro, A673V shifts β-secretase processing of APP toward the amyloidogenic pathway and increases Aβ aggregation; however, co-incubation of mutant and wild-type Aβ inhibits amyloidogenesis and toxicity. | Coding Exon 16 |
Point, Missense GCA to GTA |
0 | Di Fede et al., 2009 | |
H677R (English) |
Alzheimer's Disease | AD : Not Classified | Unknown. | Accelerated oligomerization kinetics and greater cytotoxicity than wild-type Aβ. | rs63749953 |
Coding Exon 16 |
Point, Missense CAT to CGT |
0 | Janssen et al., 2003 |
D678H (Taiwanese) |
Alzheimer's Disease | AD : Pathogenic | Unknown; SPECT imaging showed hypoperfusion in the bilateral parietal cortices and the left temporal lobe. | Increased Aβ42/Aβ40 ratio in conditioned media; increased secreted Aβ42 and Aβ40. When coincubated with Cu2+ and Zn2+, mutant Aβ exhibits increased metal ion binding and formation of ion-induced Aβ oligomers. Increased toxicity in vitro compared with wild-type Aβ42. | Coding Exon 16 |
Point, Missense GAC to CAC |
0 | Chen et al., 2012 | |
D678N (Tottori) |
Alzheimer's Disease | AD : Pathogenic | Marked cortical atrophy, bilateral hippocampal atrophy, absence of focal cerebral infarction or hemorrhagic lesions in heterozygous carrier; small lacunar lesions in temporoparietal cortex and subcortical white matter in homozygous carrier. | Accelerated oligomerization kinetics and greater cytotoxicity than wild-type Aβ. | rs63750064 |
Coding Exon 16 |
Point, Missense GAC to AAC |
0 | Wakutani et al., 2004 |
E682K (Leuven) |
Alzheimer's Disease | AD : Not Classified | Bilateral hippocampal volume loss; Cortical PiB uptake. | Significantly increased total Aβ and Aβ42/Aβ40 levels; Shifts BACE1 cleavage toward the β-site. | Coding Exon 16 |
Point, Missense GAA to AAA |
0 | Zhou et al., 2011 | |
K687Q |
Alzheimer's Disease | AD : Likely Pathogenic | Unknown, but imaging revealed white matter hyperintensities. | Unknown, but predicted to be probably damaging by PolyPhen-2 and tolerated by SIFT. | Coding Exon 16 |
Point, Missense AAA to CAA |
0 | Jiang et al., 2019; Yi et al., 2020 |
|
K687N |
Alzheimer's Disease | AD : Not Classified | Unknown; MRI showed mild global brain atrophy without focal or vascular lesions. CSF biomarker profile consistent with AD, specifically elevated total tau and phosphorylated tau, along with reduced levels of Aβ1-42. | Reduces APP cleavage by α-secretase. Reduced production of total sAPP and especially sAPPα. Increased Aβ40 and Aβ42. Alone, mutant Aβ was less toxic to neuroblastoma cells than wild-type Aβ42, but mixed in equimolar amounts with wild-type, toxicity increased. Alone, mutant Aβ formed predominantly low-n oligomers in vitro, but mixed with wild-type Aβ, it aggregated into high-n oliogmers. | Coding Exon 16 |
Point, Missense AAA to AAT |
0 | Kaden et al., 2012 | |
L688V |
Alzheimer's Disease, Cerebral Amyloid Angiopathy, Vascular Dementia | VaD : Likely Pathogenic | In one case, CADASIL-like pathology with CAA was observed. In another, white matter damage and brain atrophy, particularly in the temporal lobe and hippocampus, were reported. CSF biomarkers were consistent with AD 4 years afterwards. | Unknown. Although several lines of evidence suggest the variant is damaging, its PHRED-scaled CADD score was <20. | Coding Exon 16 |
Point, Missense TTG to GTG |
0 | Psychogios et al., 2021; Kalampokini et al., 2021 |
|
A692G (Flemish) |
Alzheimer's Disease | AD : Pathogenic | β-amyloid deposition in the blood vessels of the brain; Numerous senile plaques; Dystrophic neurites; Congophilic angiopathy; Hemorrhagic infarction. | Increased secreted Aβ42 and Aβ40 in CHO, HEK-293, and H4 cells; Altered APP processing. | rs63750671 |
Coding Exon 17 |
Point, Missense GCA to GGA |
0 | Hendriks et al., 1992 |
E693Q (Dutch) |
Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type | CAA : Pathogenic | Extensive amyloid deposition in the cerebral vasculature; Hemorrhages; Some diffuse plaques in brain parenchyma. | Accelerates Aβ aggregation in vitro, increasing fibril formation; Alters the processing of APP, increasing the relative quantities of Aβ beginning at Asp1, Val18, and Phe19. | rs63750579 |
Coding Exon 17 |
Point, Missense GAA to CAA |
4 | Levy et al., 1990; Van Broeckhoven et al., 1990; Fernandez-Madrid et al., 1991 |
E693K (Italian) |
Cerebral Amyloid Angiopathy | CAA : Pathogenic | Small to large hematomas, subarachnoid bleeding, scars with hemosiderin deposits, small infarcts; Aβ immunoreactivity in vessel walls and neuropil; Absence of neurofibrillary changes and neuritic plaques. | Reduced Aβ42/Aβ40 ratio; decreased Aβ42; comparable Aβ40 to wild-type APP. | rs63750579 |
Coding Exon 17 |
Point, Missense GAA to AAA |
0 | Tagliavini et al., 1999; Bugiani et al., 2010 |
E693G (Arctic) |
Alzheimer's Disease | AD : Pathogenic | No signs of strokes or vascular lesions by brain imaging; Neuritic plaques and neurofibrillary tangles. | Arctic Aβ40 forms protofibrils at an increased propensity and faster rate; Decreased proteolytic degradation of Aβ by neprilysin. | rs63751039 |
Coding Exon 17 |
Point, Missense GAA to GGA |
8 | Kamino et al., 1992; Nilsberth et al., 2001 |
E693del (Osaka, E693∆, E693delta) |
Alzheimer's Disease | AD : Pathogenic | Unknown; remarkably low levels of amyloid by PiB-PET imaging. | Unchanged Aβ42/Aβ40 ratio; decreased Aβ42; decreased Aβ40; Mutant Aβ more resistant to degradation by neprilysin and insulin-degrading enzyme; Synthetic mutant Aβ had enhanced oligomerization but no fibrillization; Greater inhibition of LTP than wild-type Aβ. | Coding Exon 17 |
Deletion GAA to --- |
1 | Tomiyama et al., 2008 | |
D694N (Iowa) |
Cerebral Amyloid Angiopathy, Dementia, Vascular Dementia | VaD : Pathogenic | Extensive cerebral amyloid angiopathy; Widespread neurofibrillary tangles; Abundant Aβ40 in plaques; Hemorrhagic lesions; Cortical calcifications in the occipital lobe. | Increased fibrillogenesis of the Aβ peptide; Greater Aβ-induced toxicity. | rs63749810 |
Coding Exon 17 |
Point, Missense GAT to AAT |
2 | Grabowski et al., 2001 |
V695M |
Alzheimer's Disease | AD : Not Classified | Unknown. | Unknown. In silico algorithms yielded mixed results, but integrative PHRED-scaled CADD score was > 20, suggesting deleterious effect. | Coding Exon 17 |
Point, Missense GTG to ATG |
0 | Gao et al., 2019 | |
F690_V695del (Uppsala deletion) |
Alzheimer's Disease | AD : Pathogenic | One reported carrier of this variant had autopsy-confirmed AD. | Appears to largely eliminate non-amyloidogenic processing of APP and leads to the generation of rapidly aggregating Aβ peptides lacking amino acids 19-24. | Coding Exon 17 |
Deletion TTC.TTT.GCA.GAA.GAT.GTG to ---.---.---.---.---.--- |
0 | Pagnon de la Vega et al., 2021 | |
L705V |
Cerebral Amyloid Angiopathy | CAA : Likely Pathogenic | Severe CAA; Hemorrhages originating from affected vessels; “Vessel-within-vessel” morphology; Absence of parenchymal amyloid deposits and neurofibrillary tangles. | Unknown. | rs63750921 |
Coding Exon 17 |
Point, Missense CTC to GTC |
0 | Obici et al., 2005 |
G708G |
None | AD : Benign | Not applicable. | Increased Aβ42 secretion without significantly affecting the Aβ42/Aβ40 ratio in cells. | rs148888161 |
Coding Exon 17 |
Point, Silent GGC to GGT |
0 | Balbín et al., 1992 |
G709S |
Parkinson's Disease Dementia | PDD : Not Classified | Unknown. | Unknown, but in silico analysis predicted it is deleterious (PHRED-scaled CADD score >20). | rs201269325 |
Coding Exon 17 |
Point, Missense GGT to AGT |
0 | Schulte et al., 2015 |
A713T |
Alzheimer's Disease, Cerebral Amyloid Angiopathy, None | AD : Uncertain Significance | Variable: Generalized atrophy of the cerebral cortex; Widespread neurofibrillary tangles; Neuritic plaques; Variable cerebral amyloid angiopathy. | Increased Aβ42/Aβ40 ratio due to decreased Aβ40 secretion in cells. | rs63750066 |
Coding Exon 17 |
Point, Missense GCG to ACG |
0 | Carter et al., 1992; Armstrong et al., 2004 |
A713V |
None | AD : Benign | Not applicable. | Decreased Aβ42 and Aβ40 secretion in cells; no effect on Aβ42/Aβ40 ratio. | rs1800557 |
Coding Exon 17 |
Point, Missense GCG to GTG |
0 | Jones et al., 1992 |
T714A (Iranian) |
Alzheimer's Disease | AD : Pathogenic | Progressive cortical atrophy; White matter lesions. | Unknown, but predicted deleterious by in silico algorithms (PHRED-scaled CADD score > 20). | rs63750643 |
Coding Exon 17 |
Point, Missense ACA to GCA |
0 | Pasalar et al., 2002 |
T714I (Austrian) |
Alzheimer's Disease | AD : Pathogenic | Extensive neuronal loss; Diffuse gliosis; Neurofibrillary tangles; Amyloid plaques including diffuse "cloudy" plaques. | Increased Aβ42/Aβ40 ratio (about 11-fold); increased Aβ42; decreased Aβ40. | rs63750973 |
Coding Exon 17 |
Point, Missense ACA to ATA |
2 | Kumar-Singh et al., 2000 |
V715M (French) |
Alzheimer's Disease | AD : Pathogenic | Progressive cortical atrophy; Hypometabolism. | Decreased total Aβ; unchanged Aβ42; significantly decreased Aβ40. | rs63750734 |
Coding Exon 17 |
Point, Missense GTG to ATG |
0 | Ancolio et al., 1999 |
V715A (German) |
Alzheimer's Disease | AD : Pathogenic | Hypoperfusion in the parieto-occipital region. | Increased Aβ42/Aβ40 ratio. | rs63750868 |
Coding Exon 17 |
Point, Missense GTG to GCG |
0 | Cruts et al., 2003 |
I716F |
Alzheimer's Disease | AD : Pathogenic | Extensive mixed neuropathology, including neurofibrillary changes, amyloid deposits, and Lewy bodies. | Increased Aβ42/Aβ40 ratio; increased Aβ42; decreased Aβ40; Increased APP C-terminal fragments; Decreased production of APP intracellular domain. | Coding Exon 17 |
Point, Missense ATC to TTC |
4 | Guerreiro et al., 2010 | |
I716V (Florida) |
Alzheimer's Disease | AD : Not Classified | Diffuse cortical atrophy, most prominant in the left anterior temporal lobe. | Increased Aβ42(43)/Aβ40 ratio; increased Aβ42(43). | rs63750399 |
Coding Exon 17 |
Point, Missense ATC to GTC |
11 | Eckman et al., 1997 |
I716T |
Alzheimer's Disease | AD : Not Classified | Unknown. | Unknown, but in silico analysis predicted a damaging effect (PHRED-scaled CADD score > 20). | rs63750851 |
Coding Exon 17 |
Point, Missense ATC to ACC |
0 | Terreni et al., 2002 |
I716M |
Alzheimer's Disease | AD : Not Classified | Unknown; MRI showed mild bilateral hippocampal atrophy. | Unknown; predicted damaging in silico (PHRED-scaled CADD score > 20). | Coding Exon 17 |
Point, Missense ATC to ATG |
0 | Blauwendraat et al., 2016 | |
V717F (Indiana) |
Alzheimer's Disease | AD : Pathogenic | In one case, neuropathology was consistent with AD. | Increased Aβ42/Aβ40 ratio. | rs63750264 |
Coding Exon 17 |
Point, Missense GTC to TTC |
13 | Murrell et al., 1991 |
V717L |
Alzheimer's Disease | AD : Pathogenic | Unknown; MRI in the Japanese family showed relatively minor atrophic changes in the bilateral hippocampus and cerebral cortices. | Increased Aβ42/Aβ40 ratio; increased Aβ42; decreased Aβ40. | rs63750264 |
Coding Exon 17 |
Point, Missense GTC to CTC |
0 | Murrell et al., 2000 |
V717I (London) |
Alzheimer's Disease | AD : Pathogenic | Variable: some reports of mild amyloid angiopathy and cortical and brainstem Lewy bodies, along with numerous plaques and tangles. | Increased Aβ42/Aβ40 ratio; increased Aβ42; little effect on Aβ40. | rs63750264 |
Coding Exon 17 |
Point, Missense GTC to ATC |
23 | Goate et al., 1991 |
V717G |
Alzheimer's Disease | AD : Pathogenic | Neuropathology consistent with AD in at least one case. | Increased Aβ42/Aβ40 ratio; increased Aβ42; decreased Aβ40. | rs63749964 |
Coding Exon 17 |
Point, Missense GTC to GGC |
0 | Chartier-Harlin et al., 1991 |
T719P |
Alzheimer's Disease | AD : Not Classified | Unknown; atrophy of the temporal lobes by MRI. | Reduced total Aβ in CSF, especially Aβ1-40 and Aβ1-42 with a relative increase in Aβ1-38. | Coding Exon 17 |
Point, Missense ACC to CCC |
0 | Ghidoni et al., 2009 | |
T719N |
Alzheimer's Disease | AD : Pathogenic | Unknown. | In a heterologous expression system, the T719N mutation led to increased levels of Aβ42 and an elevated Aβ42:Aβ40 ratio, compared with wild-type APP. | Coding Exon 17 |
Point, Missense ACC to AAC |
0 | Hsu et al., 2018 | |
M722K |
Alzheimer's Disease, None | AD : Pathogenic | Unknown; MRI of the proband at age 42 showed moderate cerebral atrophy, especially in the hippocampus. | Increase Aβ42/Aβ40 ratio; increased Aβ42; unchanged Aβ40; More phospho-tau. | Coding Exon 17 |
Point, Missense ATG to AAG |
0 | Wang et al., 2015 | |
L723P (Australian) |
Alzheimer's Disease | AD : Pathogenic | Unknown. | Increased Aβ42 in CHO cells. | rs63751122 |
Coding Exon 17 |
Point, Missense CTG to CCG |
0 | Kwok et al., 2000 |
K724N (Belgian) |
Alzheimer's Disease | AD : Not Classified | Significant amyloid across the cerebral cortex as measured by PiB-PET. | Increased Aβ42/Aβ40 ratio; increased Aβ42; decreased Aβ40. | rs63750151 |
Coding Exon 17 |
Point, Missense AAG to AAC |
0 | Theuns et al., 2006 |
H733P |
None | AD : Not Classified | Not applicable. | Increased Aβ42 moderately, without significantly altering the Aβ42/Aβ40 ratio in cells. | Coding Exon 17 |
Point, Missense CAT to CCT |
0 | Guerreiro et al., 2010 | |
IVS17 83-88delAAGTAT |
Alzheimer's Disease, None | AD : Benign | Unknown; at least one affected deletion carrier had neuropathology consistent with AD. | Unknown; deletion does not appear to affect APP splicing. | rs367709245 |
Non-Coding Intron 17 |
Deletion |
0 | Kamino et al., 1992 |
c.*18 C>T |
Cerebral Amyloid Angiopathy | CAA : Likely Benign | Unknown; imaging showed an ischemic stroke in the right middle cerebral artery and hematomas in the right temporal and parietal lobes. MRI showed numerous cortical microbleeds and white-matter hyperintensities. | Unknown. Failed to reach commonly used threshold for in silico deleteriousness classification (PHRED-scaled CADD score = 19.09). | rs201729239 |
Non-Coding 3' UTR |
Point |
0 | Nicolas et al., 2015 |
c.*331_*332del |
Cerebral Amyloid Angiopathy | CAA : Likely Pathogenic | Unknown; imaging revealed multiple subarachnoid hemorrhages and hematomas in the temporal, frontal, and parietal regions of the cortex, as well as diffuse superficial siderosis, cortical microbleeds, and white matter hyperintensities. | This deletion of two base pairs (TA) occurs in a highly conserved region of the UTR. When cloned into a luciferase reporter, the variant increased APP expression (~1.5-fold over WT). APP upregulation was at least partially attributable to changes in miRNA binding. | Non-Coding 3' UTR |
Deletion |
0 | Nicolas et al., 2015 | |
c.*372 A>G |
Cerebral Amyloid Angiopathy | CAA : Benign | Unknown; at least two mutation carriers had hemorrhages and microbleeds consistent with CAA. However, this variant has also been detected in controls. | Unknown. | rs187940037 |
Non-Coding 3' UTR |
Point |
0 | Nicolas et al., 2015 |