Search Results

PSEN2 (53)

Mutation	Clinical Phenotype	Pathogenicity	Neuropathology	Biological Effect	Genomic Position	Genomic Region	Mutation Type Codon Change	Research Models	Primary Papers
T18M	Parkinson's Disease	PD : Unclear Pathogenicity	Unknown.	Unknown; predicted pathogenic in silico.	rs143061887	Coding Exon 3	Point, Missense ACG to ATG	0	Blauwendraat et al., 2016
R29H	None	AD : Not Pathogenic	Not applicable.	Unknown.		Coding Exon 3	Point CGC to CAC	0	Guerreiro et al., 2010
G34S	Alzheimer's Disease	AD : Unclear Pathogenicity	Unknown.	Unchanged Aβ42/Aβ40 ratio.		Coding Exon 3	Point GGC to AGC	0	Sleegers et al., 2004
R62C	Alzheimer's Disease, None	AD : Unclear Pathogenicity	Unknown.	Unknown; predicted possibly damaging in silico.	rs150400387	Coding Exon 4	Point CGC to TGC	0	Sleegers et al., 2004; Ertekin-Taner et al., 2008; Brouwers et al., 2008
R62H	Alzheimer's Disease, Frontotemporal Dementia, Parkinson's Disease Dementia	AD : Not Pathogenic, FTD : Not Pathogenic	Unknown.	Unchanged Aβ42/Aβ40 ratio; unchanged Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF.	rs58973334	Coding Exon 4	Point, Missense CGC to CAC	0	Cruts et al., 1998; Gallo et al., 2010
P69A	Alzheimer's Disease	AD : Unclear Pathogenicity	Unknown.	Unknown.		Coding Exon 4	Point, Missense CCC to GCC	0	Dobricic et al., 2012
R71W	Alzheimer's Disease, None, Parkinson's Disease Dementia	AD : Not Pathogenic	Leukoencephalopathy with periventricular white-matter lacunar infarctions.	Unchanged Aβ42/Aβ40 ratio; Reduces the stability of the presenilin-2 protein and impairs Notch signaling.	rs140501902	Coding Exon 4	Point, Missense CGG to TGG	0	Sleegers et al., 2004
K82R	Alzheimer's Disease	AD : Unclear Pathogenicity	Unknown; neuroimaging showed diffuse cortical atrophy, especially in the posterior region and mild hippocampal atrophy. FDG-PET showed widespread hypometabolism. PIB-PET showed amyloid deposition in the frontal lobe, lateral temporal lobe, parietal lobe, posterior cingulate cortex, precuneus, and striatum.	Unknown.		Coding Exon 4	Point, Missense AAA to AGA	0	Shi et al., 2015
A85V	Alzheimer's Disease, Dementia with Lewy Bodies	AD : Pathogenic, DLB : Unclear Pathogenicity	Amyloid deposition; Neurofibrillary changes; Diffuse Lewy bodies in the neocortex; Bilateral basal ganglia calcifications.	Unknown.	rs63750048	Coding Exon 4	Point, Missense GCG to GTG	0	Piscopo et al., 2008
V101M	Alzheimer's Disease	AD : Unclear Pathogenicity	Unknown.	Unknown; predicted probably damaging in silico.		Coding Exon 4	Point, Missense GTG to ATG	0	Sala Frigerio et al., 2015
K115Efs*	Alzheimer's Disease	AD : Pathogenic	Neuropathology was consistent with AD.	The deletion of two nucleotides from exon 5 leads to a frameshift and ultimately to a premature stop codon in exon 6. In patient fibroblasts, secretion of Aβ40 was decreased, and Aβ38 and Aβ42 were undetectable. Wild-type PSEN2 levels were also decreased. Alternatively spliced transcripts of the mutant allele were detected in brain.		Coding Exon 4	Deletion AAG to A--	0	Jayadev et al., 2010
T122P	Alzheimer's Disease	AD : Pathogenic	Unknown.	Increased Aβ42/Aβ40 ratio; increased Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF.	rs63749851	Coding Exon 5	Point, Missense ACG to CCG	0	Finckh et al., 2000
T122R	Atypical Dementia	Atypical Dementia : Pathogenic	Variable cortical and subcortical atrophy.	Reduced calcium ion released from intracellular stores.	rs28936380	Coding Exon 5	Point, Missense ACG to AGG	0	Binetti et al., 2003
P123L	Alzheimer's Disease	AD : Unclear Pathogenicity	Unknown; Neuroimaging showed diffuse cortical atrophy, predominantly in the right hemisphere. FDG-PET showed hypoperfusion in the right temporal and parietal regions.	Unknown; predicted probably damaging in silico.		Coding Exon 5	Point, Missense CCA to CTA	0	Xia et al., 2015
E126fs	Alzheimer's Disease	AD : Unclear Pathogenicity	Unknown; neuroimaging showed hippocampal and parahippocampal atrophy.	Unknown; the insertion of one nucleotide (A) is predicted to result in a frameshift at codon 126.		Coding Exon 5	Insertion GAG.GAC to GAA.GGA	0	El Kadmiri et al., 2014
E126K	Alzheimer's Disease	AD : Pathogenic	Unknown.	Unknown; predicted probably damaging in silico.		Coding Exon 5	Point, Missense GAG to AAG	0	Müller et al., 2014
S130L	Alzheimer's Disease, None, Parkinson's Disease Dementia	AD : Unclear Pathogenicity	Neuropathology consistent with AD at autopsy in at least one case.	Unchanged Aβ42/Aβ40 ratio; unchanged Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF.	rs63750197	Coding Exon 5	Point, Missense TCG to TTG	0	Sorbi et al., 2002; Tedde et al., 2003
V139M	Alzheimer's Disease, None	AD : Unclear Pathogenicity	Bilateral hypoperfusion in the parietal-temporal lobes.	Unknown.		Coding Exon 5	Point, Missense GTG to ATG	0	Bernardi et al., 2008
N141D	Alzheimer's Disease	AD : Pathogenic	Unknown	Unknown, but 3 algorithms predict damaging with a PHRED CADD score of 24.9.		Coding Exon 5	Point, Missense AAC to GAC	0	Wang et al., 2019
N141I (Volga German)	Alzheimer's Disease	AD : Pathogenic	Extensive amyloid plaques; Extensive neurofibrillary tangles (typically a Braak score of V or VI); α-synuclein inclusions, especially in the amygdala; Rare TDP-43 pathology; Hippocampal sclerosis.	Increased Aβ42/Aβ40 ratio; increased Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF.	rs63750215	Coding Exon 5	Point, Missense AAC to ATC	5	Levy-Lahad et al., 1995; Rogaev et al., 1995
N141Y	Alzheimer's Disease	AD : Pathogenic	Proband had autopsy-confirmed AD with severe brain atrophy and numerous plaques and neurofibrillary tangles.	Unknown; predicted damaging in silico.	rs61761208	Coding Exon 5	Point, Missense AAC to TAC	0	Niu et al., 2014
L143H	None	AD : Not Pathogenic	Not applicable.	Unknown.		Coding Exon 5	Point, Missense CTC to CAC	0	Guerreiro et al., 2010
V148I	Alzheimer's Disease	AD : Unclear Pathogenicity	Unknown.	Unchanged Aβ42/Aβ40 ratio; unchanged Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF.	rs63750812	Coding Exon 5	Point, Missense GTC to ATC	0	Lao et al., 1998
K161R	Alzheimer's Disease	AD : Pathogenic	Unknown.	Unknown.		Coding Exon 5	Point, Missense AAG to AGG	0	Wallon et al., 2012
R163H	None	AD : Not Pathogenic	Not applicable.	Unknown.		Coding Exon 5	Point, Missense CGC to CAC	0	Puschmann et al., 2009
H169N	Alzheimer's Disease, Frontotemporal Dementia, Progressive Nonfluent Aphasia	AD : Unclear Pathogenicity, FTD : Unclear Pathogenicity	Unknown; neuroimaging showed mild atrophy and widespread hypometabolism. PIB-PET showed amyloid deposition in the AD case, but no amyloid deposition in the FTD case.	Unknown.		Coding Exon 6	Point, Missense CAT to AAT	0	Shi et al., 2015
M174V	Alzheimer's Disease, Frontotemporal Dementia	AD : Not Pathogenic	Unknown; imaging has shown frontal atrophy and hypoperfusion in temporoparietal regions.	Unknown; predicted benign in silico.	rs61757781	Coding Exon 6	Point, Missense ATG to GTG	0	Andreoli et al., 2008; Clarimón et al., 2008; Guerreiro et al., 2010
S175C	Alzheimer's Disease	AD : Pathogenic	Unknown; MRI showed focal atrophy in the medial temporal lobe; SPECT showed bilateral hypoperfusion in temporoparietal regions.	Unknown.		Coding Exon 6	Point, Missense TCT to TGT	0	Piscopo et al., 2010
G212V	Alzheimer's Disease	AD : Pathogenic	Neuropathology consistent with AD.	Unknown; predicted pathogenic in silico.		Coding Exon 7	Point, Missense GGG to GTG	0	Marín-Muñoz et al., 2016
V214L	Alzheimer's Disease	AD : Unclear Pathogenicity	Unknown; neuroimaging showed diffuse cortical atrophy and widespread hypometabolism.	Unknown; structural changes were predicted in silico, especially at amino acids 214, 219, and 220. PolyPhen2 predicted a probably or possibly damaging effect.		Coding Exon 7	Point, Missense GTG to TTG	0	Youn et al., 2014
Q228L	Alzheimer's Disease	AD : Unclear Pathogenicity	Unknown.	Unknown.	rs63750880	Coding Exon 7	Point, Missense CAG to CTG	0	Zekanowski et al., 2003
Y231C	Frontotemporal Dementia	FTD : Pathogenic	Unknown; MRI showed diffuse subcortical and cortical atrophy, particularly in the frontotemporoparietal lobes.	Unknown.		Coding Exon 7	Point, Missense TAC to TGC	0	Marcon et al., 2009
I235F	Alzheimer's Disease, None	AD : Not Pathogenic	Not applicable.	Unknown.		Coding Exon 7	Point, Missense ATC to TTC	0	Lee et al., 2014
A237V	Alzheimer's Disease	AD : Unclear Pathogenicity	Neuropathology consistent with AD.	Unknown; predicted possibly damaging in silico.	rs200670135	Coding Exon 7	Point, Missense GCG to GTG	0	Sassi et al., 2014
L238F	Alzheimer's Disease	AD : Unclear Pathogenicity	Unknown.	Unknown; predicted probably damaging in silico.		Coding Exon 7	Point, Missense CTC to TTC	0	Sala Frigerio et al., 2015
L238P	Alzheimer's Disease	AD : Unclear Pathogenicity	Unknown; MRI showed supratentorial cortical atrophy, particularly atrophy of the parietal cortex.	Unknown; predicted damaging in silico.		Coding Exon 8	Point, Missense CTC to CCC	0	Blauwendraat et al., 2016
M239I	Alzheimer's Disease	AD : Pathogenic	Moderate cortical atrophy; Numerous neurofibrillary tangles; Numerous senile plaques, especially in the amygdala.	Increased Aβ42/Aβ40 ratio; increased Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF; Reduced calcium release.	rs63749884	Coding Exon 7	Point, Missense ATG to ATA	0	Finckh et al., 2000
M239V	Alzheimer's Disease	AD : Pathogenic	Diffuse cerebral atrophy; Senile plaques; Neurofibrillary tangles (stage VI of Braak and Braak); Ectopic neurons in the subcortical white matter; Extracellular "ghost" neurofibrillary tangles.	Increased Aβ42/Aβ40 ratio; increased Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF.	rs28936379	Coding Exon 7	Point, Missense ATG to GTG	0	Rogaev et al., 1995
A252T	None	AD : Not Pathogenic	Not applicable.	Unknown.	rs138836272	Coding Exon 7	Point, Missense GCG to ACG	0	Guerreiro et al., 2010
A258T	None	AD : Not Pathogenic	Not applicable.	Unknown.	rs148238688	Coding Exon 7	Point, Missense GCC to ACC	0	Sala Frigerio et al., 2015
A258V	Alzheimer's Disease	AD : Unclear Pathogenicity	Unknown	Predicted not pathogenic in silico.	rs14443227784	Coding Exon 7	Point, Missense GCC to GTC	0	Yagi et al., 2014
T301M	Alzheimer's Disease	AD : Unclear Pathogenicity	Unknown.	Unchanged Aβ42/Aβ40 ratio.	rs144277432	Coding Exon 7	Point, Missense ACG to ATG	0	Croes et al., 2004
K306fs	Alzheimer's Disease	AD : Unclear Pathogenicity	Unknown; neuroimaging showed cortical atrophy.	Unknown; the deletion of a single nucleotide (A) in exon 9 is predicted to result in a frameshift at codon 306.		Coding Exon 9	Deletion AAG.CTG to AGC.TGG	0	El Kadmiri et al., 2014
P334A	Alzheimer's Disease, None	AD : Not Pathogenic	Not applicable.	Unknown.		Coding Exon 10	Point, Missense CCT to GCT	0	Lee et al., 2014
P334R	Alzheimer's Disease, None	AD : Not Pathogenic	Not applicable.	Unknown.	rs63750207	Coding Exon 10	Point, Missense CCT to CGT	0	Lleó et al., 2002
P348L	Alzheimer's Disease	AD : Unclear Pathogenicity	Unknown.	Unknown.		Coding Exon 10	Point, Missense CCA to CTA	0	Blauwendraat et al., 2016
A377V	Alzheimer's Disease, None	AD : Not Pathogenic	Not applicable.	Unknown.		Coding Exon 11	Point, Missense GCG to GTG	0	Lee et al., 2014
A379D	Alzheimer's Disease	AD : Pathogenic	Unknown	Unknown, but predicted damaging in silico. PHREDD CADD score = 27.1		Coding Exon 11	Point, Missense GCC to GAC	0	Wang et al., 2019
V393M	Alzheimer's Disease	AD : Unclear Pathogenicity	Unknown; bilateral hypometabolism in the parieto-occipital regions.	Unchanged Aβ42/Aβ40 ratio; unchanged Aβ42.	rs142690225	Coding Exon 11	Point, Missense GTG to ATG	0	Lindquist et al., 2008
T421M	Alzheimer's Disease	AD : Pathogenic	Unknown	Predicted to be pathogenic in silico (SIFT, PolyPhen2, Pmut).	rs756609078	Coding Exon 12	Point, Missense ACG to ATG	0	Yagi et al., 2014
T430M	Alzheimer's Disease	AD : Unclear Pathogenicity	Right frontotemporal hypoperfusion.	Unknown.	rs63750666	Coding Exon 12	Point, Missense ACG to ATG	0	Ezquerra et al., 2003
D439A	Alzheimer's Disease	AD : Unclear Pathogenicity	Unknown; imaging showed moderate cortical atrophy in the frontal and parietal regions.	Unchanged Aβ42/Aβ40 ratio; unchanged Aβ42; No change in proteolytic products PSEN2-CTF and PSEN2-NTF.	rs63750110	Coding Exon 12	Point, Missense GAC to GCC	0	Lleó et al., 2001
Intron 9/12 C>T	Alzheimer's Disease	AD : Unclear Pathogenicity	Unknown	Unknown. PHRED CADD score of 9.977.	rs1230394996	Non-Coding Intron 9/12	Point	0	Wang et al., 2019

Mutations

PSEN-2

Search Results

PSEN2 (53)