VCV000018155.26 - ClinVar

NM_000021.4(PSEN1):c.1292C>A (p.Ala431Glu)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(9)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000021.4(PSEN1):c.1292C>A (p.Ala431Glu)

Variation ID: 18155 Accession: VCV000018155.26

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 14q24.2 14: 73219177 (GRCh38) [ NCBI UCSC ] 14: 73685885 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 4, 2013	Jun 9, 2024	Feb 19, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000021.4:c.1292C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000012.1:p.Ala431Glu	missense
NM_007318.3:c.1280C>A	NP_015557.2:p.Ala427Glu	missense
NC_000014.9:g.73219177C>A
NC_000014.8:g.73685885C>A
NG_007386.2:g.87707C>A
LRG_224:g.87707C>A
LRG_224t1:c.1292C>A	LRG_224p1:p.Ala431Glu
	P49768:p.Ala431Glu

... more HGVS ... less HGVS

Protein change

A431E, A427E

Other names

Canonical SPDI

NC_000014.9:73219176:C:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Trans-Omics for Precision Medicine (TOPMed) 0.00001

Links

OMIM: 104311.0033 dbSNP: rs63750083 ClinGen: CA341492 UniProtKB: P49768#VAR_025605 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
PSEN1		-	-	GRCh38 GRCh37	529	546

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Alzheimer disease 3	Pathogenic (4)	criteria provided, multiple submitters, no conflicts	Feb 19, 2024	RCV000019785.41
Acne inversa, familial, 3 Alzheimer disease 3 Frontotemporal dementia Pick disease	Pathogenic (1)	criteria provided, single submitter	Jan 5, 2024	RCV000640606.17
not provided	Pathogenic (4)	criteria provided, multiple submitters, no conflicts	Dec 19, 2023	RCV000517533.22

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Sep 10, 2023)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001811424.2 First in ClinVar: Sep 08, 2021 Last updated: Sep 22, 2023	Comment: Published functional studies demonstrate a damaging effect (Nelson et al., 2010; Sun et al., 2017); In silico analysis supports that this missense variant has a … (more) Published functional studies demonstrate a damaging effect (Nelson et al., 2010; Sun et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27614114, 20634584, 20145736, 27930341, 26756738, 30716424, 11524469, 16628450, 16801675, 16897084, 31884479, 33274538) (less)
Pathogenic (Oct 30, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV002048085.2 First in ClinVar: Jan 08, 2022 Last updated: Feb 20, 2024	Comment: The PSEN1 c.1292C>A; p.Ala431Glu (rs63750083) variant is reported in the literature in several individuals and families with Alzheimer's disease (Parker 2019, Portelius 2010, Soosman 2016) … (more) The PSEN1 c.1292C>A; p.Ala431Glu (rs63750083) variant is reported in the literature in several individuals and families with Alzheimer's disease (Parker 2019, Portelius 2010, Soosman 2016) and is implicated as a founder variant in individuals from Jalisco state in Mexico (Murrell 2006). The variant is reported in the ClinVar database as pathogenic by several sources (Variation ID: 18155) but is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. The alanine at codon 431 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.946). Functional studies indicate this variant inhibits gamma secretase activity and impair its function as a calcium leak channel (Nelson 2010, Sun 2017). Based on available information, this variant is classified as pathogenic. References: Murrell J et al. The A431E mutation in PSEN1 causing familial Alzheimer's disease originating in Jalisco State, Mexico: an additional fifteen families. Neurogenetics. 2006 Nov;7(4):277-9. Nelson O et al. Familial Alzheimer's disease mutations in presenilins: effects on endoplasmic reticulum calcium homeostasis and correlation with clinical phenotypes. J Alzheimers Dis. 2010;21(3):781-93. Parker J et al. Homozygosity for the A431E mutation in PSEN1 presenting with a relatively aggressive phenotype. Neurosci Lett. 2019 Apr 23;699:195-198. Portelius E et al. Distinct cerebrospinal fluid amyloid beta peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease. Mol Neurodegener. 2010 Jan 14;5:2. Soosman SK et al. Widespread white matter and conduction defects in PSEN1-related spastic paraparesis. Neurobiol Aging. 2016 Nov;47:201-209. Sun L et al. Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of AB42 and AB40 peptides by gamma-secretase. Proc Natl Acad Sci U S A. 2017 Jan 24;114(4):E476-E485. (less)
Pathogenic (Jan 05, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Alzheimer disease 3 Pick disease Acne inversa, familial, 3 Frontotemporal dementia Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000762200.8 First in ClinVar: May 28, 2018 Last updated: Feb 28, 2024	Publications: PubMed (7) PubMed: 28492532‚ 16628450‚ 16897084‚ 20145736‚ 20634584‚ 21373759‚ 27930341 Comment: This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 431 of the PSEN1 protein … (more) This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 431 of the PSEN1 protein (p.Ala431Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant Alzheimer disease (PMID: 16628450, 16897084). It is commonly reported in individuals of Mexican ancestry (PMID: 16628450, 16897084). ClinVar contains an entry for this variant (Variation ID: 18155). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PSEN1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects PSEN1 function (PMID: 20145736, 20634584, 21373759, 27930341). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Feb 19, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Alzheimer disease 3 Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV005049466.1 First in ClinVar: Jun 09, 2024 Last updated: Jun 09, 2024
Pathogenic (Mar 08, 2022)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	Alzheimer disease 3 Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV002500189.1 First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022	Publications: PubMed (3) PubMed: 16897084‚ 20145736‚ 27930341 Comment: Variant summary: PSEN1 c.1292C>A (p.Ala431Glu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more) Variant summary: PSEN1 c.1292C>A (p.Ala431Glu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251436 control chromosomes. c.1292C>A has been widely reported in the literature in multiple individuals affected with Alzheimer Disease, Type 3 and is regarded as a founder variant of Mexican origin (example, Murrell_2006). These data indicate that the variant is very likely to be associated with disease. At least two publications report experimental evidence evaluating an impact on protein function demonstrating a modulation of the gamma secretase activity and an increased ratio of long A-beta APP (amyloid precursor protein) cleavage fragments over shorter ones, exemplified by the ratio of A-beta42 over A-beta 40, consistent with the established pathophysiology of disease (example, Portelius_2010, Sun_2017). Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
Pathogenic (May 16, 2022)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Athena Diagnostics Accession: SCV000614819.3 First in ClinVar: Dec 19, 2017 Last updated: Dec 31, 2022	Publications: PubMed (22) PubMed: 16897084‚ 20634584‚ 16628450‚ 19915487‚ 21373759‚ 19196715‚ 23341831‚ 25959826‚ 16116115‚ 22689192‚ 14966176‚ 21952501‚ 24093083‚ 20729396‚ 19021905‚ 27930341‚ 30716424‚ 27614114‚ 33274538‚ 33188013‚ 11524469‚ 20145736 Comment: This variant has been identified in multiple unrelated individuals with autosomal dominant Alzheimer disease and is considered the most common cause of Alzheimer disease among … (more) This variant has been identified in multiple unrelated individuals with autosomal dominant Alzheimer disease and is considered the most common cause of Alzheimer disease among individuals of Mexican ancestry (PMID: 16628450, 16897084, 33274538). This variant has not been reported in large, multi-ethnic general populations. (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)) At least one other missense variant at this codon is considered to be pathogenic or likely pathogenic, suggesting this variant may also cause disease. Assessment of experimental evidence suggests this variant results in abnormal protein function. A study shows this variant results in increased amyloid-beta 42 peptide production (PMID: 27930341). (less)
Pathogenic (Dec 19, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV002024760.3 First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024
Pathogenic (Nov 01, 2006)	no assertion criteria provided Method: literature only	ALZHEIMER DISEASE, FAMILIAL, 3 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000040083.3 First in ClinVar: Apr 04, 2013 Last updated: May 15, 2017	Publications: PubMed (2) PubMed: 16628450‚ 16897084 Comment on evidence: In affected members of 9 Mexican families with early-onset Alzheimer disease-3 (AD3; 607822), Yescas et al. (2006) identified a heterozygous mutation in exon 12 of … (more) In affected members of 9 Mexican families with early-onset Alzheimer disease-3 (AD3; 607822), Yescas et al. (2006) identified a heterozygous mutation in exon 12 of the PSEN1 gene, resulting in an ala431-to-glu (A431E) substitution. The A431E mutation was found in 19 (32%) of 60 apparently unaffected family members, suggesting either a presymptomatic state or reduced penetrance. All families were from the state of Jalisco in western Mexico, and haplotype analysis indicated a founder effect. The A431E mutation was not identified in 100 control individuals. Murrell et al. (2006) found the A431E mutation in 20 individuals with AD3 from 15 families identified in Guadalajara, southern California, and Chicago. Age at disease onset ranged from 33 to 44 years, and spasticity was a common clinical feature. Fourteen families were of Mexican mestizo descent, and of these families, 9 could trace the illness to ancestors from the state of Jalisco in Mexico. The remaining proband had a more remote Mexican ancestry. The findings further supported a founder effect for the A431E mutation. (less)
not provided (-)	no classification provided Method: literature only	Alzheimer disease 3 Affected status: not provided Allele origin: unknown	GeneReviews Accession: SCV000040381.2 First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022	Publications: PubMed (3) PubMed: 16628450‚ 16897084‚ 20301414 BookShelf: NBK1236 BookShelf: NBK1236

Comment:

Published functional studies demonstrate a damaging effect (Nelson et al., 2010; Sun et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27614114, 20634584, 20145736, 27930341, 26756738, 30716424, 11524469, 16628450, 16801675, 16897084, 31884479, 33274538)

Comment:

The PSEN1 c.1292C>A; p.Ala431Glu (rs63750083) variant is reported in the literature in several individuals and families with Alzheimer's disease (Parker 2019, Portelius 2010, Soosman 2016) and is implicated as a founder variant in individuals from Jalisco state in Mexico (Murrell 2006). The variant is reported in the ClinVar database as pathogenic by several sources (Variation ID: 18155) but is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. The alanine at codon 431 is highly conserved, and computational analyses predict that this variant is deleterious (REVEL: 0.946). Functional studies indicate this variant inhibits gamma secretase activity and impair its function as a calcium leak channel (Nelson 2010, Sun 2017). Based on available information, this variant is classified as pathogenic. References: Murrell J et al. The A431E mutation in PSEN1 causing familial Alzheimer's disease originating in Jalisco State, Mexico: an additional fifteen families. Neurogenetics. 2006 Nov;7(4):277-9. Nelson O et al. Familial Alzheimer's disease mutations in presenilins: effects on endoplasmic reticulum calcium homeostasis and correlation with clinical phenotypes. J Alzheimers Dis. 2010;21(3):781-93. Parker J et al. Homozygosity for the A431E mutation in PSEN1 presenting with a relatively aggressive phenotype. Neurosci Lett. 2019 Apr 23;699:195-198. Portelius E et al. Distinct cerebrospinal fluid amyloid beta peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease. Mol Neurodegener. 2010 Jan 14;5:2. Soosman SK et al. Widespread white matter and conduction defects in PSEN1-related spastic paraparesis. Neurobiol Aging. 2016 Nov;47:201-209. Sun L et al. Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of AB42 and AB40 peptides by gamma-secretase. Proc Natl Acad Sci U S A. 2017 Jan 24;114(4):E476-E485.

Comment:

This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 431 of the PSEN1 protein (p.Ala431Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant Alzheimer disease (PMID: 16628450, 16897084). It is commonly reported in individuals of Mexican ancestry (PMID: 16628450, 16897084). ClinVar contains an entry for this variant (Variation ID: 18155). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PSEN1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects PSEN1 function (PMID: 20145736, 20634584, 21373759, 27930341). For these reasons, this variant has been classified as Pathogenic.

Comment:

Variant summary: PSEN1 c.1292C>A (p.Ala431Glu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251436 control chromosomes. c.1292C>A has been widely reported in the literature in multiple individuals affected with Alzheimer Disease, Type 3 and is regarded as a founder variant of Mexican origin (example, Murrell_2006). These data indicate that the variant is very likely to be associated with disease. At least two publications report experimental evidence evaluating an impact on protein function demonstrating a modulation of the gamma secretase activity and an increased ratio of long A-beta APP (amyloid precursor protein) cleavage fragments over shorter ones, exemplified by the ratio of A-beta42 over A-beta 40, consistent with the established pathophysiology of disease (example, Portelius_2010, Sun_2017). Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

Comment:

This variant has been identified in multiple unrelated individuals with autosomal dominant Alzheimer disease and is considered the most common cause of Alzheimer disease among individuals of Mexican ancestry (PMID: 16628450, 16897084, 33274538). This variant has not been reported in large, multi-ethnic general populations. (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)) At least one other missense variant at this codon is considered to be pathogenic or likely pathogenic, suggesting this variant may also cause disease. Assessment of experimental evidence suggests this variant results in abnormal protein function. A study shows this variant results in increased amyloid-beta 42 peptide production (PMID: 27930341).

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Autosomal dominant early onset Alzheimer's disease in the Mexican state of Jalisco: High frequency of the mutation PSEN1 c.1292C>A and phenotypic profile of patients.	Dumois-Petersen S	American journal of medical genetics. Part C, Seminars in medical genetics	2020	PMID: 33274538
Dedifferentiation and neuronal repression define familial Alzheimer's disease.	Caldwell AB	Science advances	2020	PMID: 33188013
Homozygosity for the A431E mutation in PSEN1 presenting with a relatively aggressive phenotype.	Parker J	Neuroscience letters	2019	PMID: 30716424
Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Aβ42 and Aβ40 peptides by γ-secretase.	Sun L	Proceedings of the National Academy of Sciences of the United States of America	2017	PMID: 27930341
Widespread white matter and conduction defects in PSEN1-related spastic paraparesis.	Soosman SK	Neurobiology of aging	2016	PMID: 27614114
Quantitative interaction proteomics of neurodegenerative disease proteins.	Hosp F	Cell reports	2015	PMID: 25959826
Subjects harboring presenilin familial Alzheimer's disease mutations exhibit diverse white matter biochemistry alterations.	Roher AE	American journal of neurodegenerative disease	2013	PMID: 24093083
Conformation-dependent oligomers in cerebrospinal fluid of presymptomatic familial Alzheimer's disease mutation carriers.	Ringman JM	Dementia and geriatric cognitive disorders extra	2012	PMID: 23341831
Plasma signaling proteins in persons at genetic risk for Alzheimer disease: influence of APOE genotype.	Ringman JM	Archives of neurology	2012	PMID: 22689192
Early-Onset Familial Alzheimer Disease – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY.	Adam MP	-	2012	PMID: 20301414
Cortical and hippocampal atrophy in patients with autosomal dominant familial Alzheimer's disease.	Apostolova LG	Dementia and geriatric cognitive disorders	2011	PMID: 21952501
Alzheimer disease-related presenilin-1 variants exert distinct effects on monoamine oxidase-A activity in vitro.	Pennington PR	Journal of neural transmission (Vienna, Austria : 1996)	2011	PMID: 21373759
Effects of risk genes on BOLD activation in presymptomatic carriers of familial Alzheimer's disease mutations during a novelty encoding task.	Ringman JM	Cerebral cortex (New York, N.Y. : 1991)	2011	PMID: 20729396
Familial Alzheimer's disease mutations in presenilins: effects on endoplasmic reticulum calcium homeostasis and correlation with clinical phenotypes.	Nelson O	Journal of Alzheimer's disease : JAD	2010	PMID: 20634584
Distinct cerebrospinal fluid amyloid beta peptide signatures in sporadic and PSEN1 A431E-associated familial Alzheimer's disease.	Portelius E	Molecular neurodegeneration	2010	PMID: 20145736
Caspase-6 activation in familial alzheimer disease brains carrying amyloid precursor protein or presenilin i or presenilin II mutations.	Albrecht S	Journal of neuropathology and experimental neurology	2009	PMID: 19915487
Mutant presenilin 1 increases the expression and activity of BACE1.	Giliberto L	The Journal of biological chemistry	2009	PMID: 19196715
Histopathological and molecular heterogeneity among individuals with dementia associated with Presenilin mutations.	Maarouf CL	Molecular neurodegeneration	2008	PMID: 19021905
The A431E mutation in PSEN1 causing familial Alzheimer's disease originating in Jalisco State, Mexico: an additional fifteen families.	Murrell J	Neurogenetics	2006	PMID: 16897084
Founder effect for the Ala431Glu mutation of the presenilin 1 gene causing early-onset Alzheimer's disease in Mexican families.	Yescas P	Neurogenetics	2006	PMID: 16628450
Neuropsychological function in nondemented carriers of presenilin-1 mutations.	Ringman JM	Neurology	2005	PMID: 16116115
Female preclinical presenilin-1 mutation carriers unaware of their genetic status have higher levels of depression than their non-mutation carrying kin.	Ringman JM	Journal of neurology, neurosurgery, and psychiatry	2004	PMID: 14966176
Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations.	Rogaeva EA	Neurology	2001	PMID: 11524469
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Text-mined citations for rs63750083 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_000021.4(PSEN1):c.1292C>A (p.Ala431Glu)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs63750083 ...