VCV000018143.28 - ClinVar

NM_000021.4(PSEN1):c.617G>C (p.Gly206Ala)

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.

(10)

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.617G>C (p.Gly206Ala)

Variation ID: 18143 Accession: VCV000018143.28

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 14q24.2 14: 73192712 (GRCh38) [ NCBI UCSC ] 14: 73659420 (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	May 15, 2017	Nov 24, 2024	Jul 30, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000021.4:c.617G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000012.1:p.Gly206Ala	missense
NM_007318.3:c.605G>C	NP_015557.2:p.Gly202Ala	missense
NC_000014.9:g.73192712G>C
NC_000014.8:g.73659420G>C
NG_007386.2:g.61242G>C
LRG_224:g.61242G>C
LRG_224t1:c.617G>C	LRG_224p1:p.Gly206Ala
	P49768:p.Gly206Ala

... more HGVS ... less HGVS

Protein change

G206A, G202A

Other names

Canonical SPDI

NC_000014.9:73192711:G:C

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.

0.00020 (C)

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

Exome Aggregation Consortium (ExAC) 0.00001

The Genome Aggregation Database (gnomAD), exomes 0.00001

The Genome Aggregation Database (gnomAD) 0.00012

1000 Genomes Project 30x 0.00016

1000 Genomes Project 0.00020

Trans-Omics for Precision Medicine (TOPMed) 0.00029

Links

ClinGen: CA258122 UniProtKB: P49768#VAR_016218 OMIM: 104311.0021 dbSNP: rs63750082 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 (2)	criteria provided, single submitter	Jul 26, 2023	RCV000019773.36
not provided	Pathogenic (5)	criteria provided, multiple submitters, no conflicts	Jul 30, 2024	RCV000518563.25
Acne inversa, familial, 3 Alzheimer disease 3 Frontotemporal dementia Pick disease	Pathogenic (1)	criteria provided, single submitter	Jan 17, 2024	RCV000640609.17
Acne inversa, familial, 3 Alzheimer disease 3 Dilated cardiomyopathy 1U Frontotemporal dementia Pick disease	Pathogenic (1)	criteria provided, single submitter	Mar 4, 2022	RCV002482890.8
PSEN1-related disorder	Pathogenic (1)	no assertion criteria provided	Sep 13, 2024	RCV004752714.1

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 (Mar 04, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Pick disease Frontotemporal dementia Alzheimer disease 3 Dilated cardiomyopathy 1U Acne inversa, familial, 3 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002777693.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Pathogenic (Aug 31, 2022)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001792148.2 First in ClinVar: Aug 21, 2021 Last updated: Sep 30, 2023	Comment: Published functional studies demonstrate a damaging effect resulting in an increase of the amyloid beta ratio (Pimenova et al., 2020); In silico analysis, which includes … (more) Published functional studies demonstrate a damaging effect resulting in an increase of the amyloid beta ratio (Pimenova et al., 2020); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 22312439, 11710891, 23383383, 22584618, 17522104, 23114514, 25333068, 11524469, 27312774, 27614114, 18797263, 26756738, 23885714, 22475797, 21952501, 20047059, 12119298, 30279455, 27073747, 27930341, 32032730) (less)
Pathogenic (Mar 06, 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: SCV002050081.2 First in ClinVar: Jan 08, 2022 Last updated: Feb 20, 2024	Comment: The PSEN1 c.617G>C; p.Gly206Ala variant (rs63750082) is reported in the literature in several individuals and families affected with early-onset Alzherimer's disease, and is a founder … (more) The PSEN1 c.617G>C; p.Gly206Ala variant (rs63750082) is reported in the literature in several individuals and families affected with early-onset Alzherimer's disease, and is a founder in the Carribean Hispanic population (Athan 2001, Arnold 2013, Lee 2014, Ravenscroft 2016, see link to Alzforum database). This variant is reported in ClinVar (Variation ID: 18143), and is only observed on three alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The glycine at codon 206 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Functional analyses of the variant protein show an impaired ability to properly cleave amyloid precursor protein, which can lead to increased amyloid plaque formation (Athan 2001, Sun 2017). Based on available information, this variant is considered to be pathogenic. References: Link to Alzforum database: https://www.alzforum.org/mutations/psen1-g206a Athan ES et al. A founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families. JAMA. 2001 Nov 14;286(18):2257-63. Arnold SE et al. Frequency and clinicopathological characteristics of presenilin 1 Gly206Ala mutation in Puerto Rican Hispanics with dementia. J Alzheimers Dis. 2013;33(4):1089-95. Lee JH et al. Disease-related mutations among Caribbean Hispanics with familial dementia. Mol Genet Genomic Med. 2014 Sep;2(5):430-7. Ravenscroft TA et al. The presenilin 1 p.Gly206Ala mutation is a frequent cause of early-onset Alzheimer's disease in Hispanics in Florida. Am J Neurodegener Dis. 2016 Mar 1;5(1):94-101. Sun L et al. Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Abeta42 and Abeta40 peptides by gamma-secretase. Proc Natl Acad Sci U S A. 2017 Jan 24;114(4):E476-E485. (less)
Pathogenic (Jan 17, 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: SCV000762203.8 First in ClinVar: May 28, 2018 Last updated: Feb 28, 2024	Publications: PubMed (9) PubMed: 28492532‚ 11524469‚ 11710891‚ 18797263‚ 22312439‚ 23114514‚ 25333068‚ 27073747‚ 27930341 Comment: This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 206 of the PSEN1 protein (p.Gly206Ala). … (more) This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 206 of the PSEN1 protein (p.Gly206Ala). This variant is present in population databases (rs63750082, gnomAD 0.003%). This missense change has been observed in individual(s) with early and late onset Alzheimer disease and Alzheimer disease (PMID: 11524469, 11710891, 18797263, 22312439, 23114514, 25333068, 27073747). It is commonly reported in individuals of Caribbean ancestry (PMID: 11524469, 11710891, 18797263, 22312439, 23114514, 25333068, 27073747). ClinVar contains an entry for this variant (Variation ID: 18143). 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 not expected to disrupt PSEN1 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects PSEN1 function (PMID: 11710891, 27930341). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Jul 26, 2023)	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: SCV004029436.1 First in ClinVar: Aug 26, 2023 Last updated: Aug 26, 2023	Publications: PubMed (1) PubMed: 11710891 Comment: Variant summary: PSEN1 c.617G>C (p.Gly206Ala) 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.617G>C (p.Gly206Ala) 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 allele was found at a frequency of 8e-06 in 251492 control chromosomes. c.617G>C has been reported in the literature in multiple individuals of Caribbean ancestry affected with Alzheimer Disease, Type 3 (Example: Athan_2001). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function indicating an increase in amyloid-beta 42 peptide production (Athan_2001). Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. The following publication have been ascertained in the context of this evaluation (PMID: 11710891). All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
Pathogenic (Mar 14, 2023)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Athena Diagnostics Accession: SCV000614823.5 First in ClinVar: Dec 19, 2017 Last updated: Jan 26, 2024	Publications: PubMed (19) PubMed: 11710891‚ 23114514‚ 22312439‚ 25333068‚ 22475797‚ 18797263‚ 26214276‚ 12119298‚ 23885714‚ 23383383‚ 11524469‚ 27930341‚ 27073747‚ 32032730‚ 31536626‚ 29874583‚ 29091718‚ 27312774‚ 26888304 Comment: This variant is statistically more frequent in individuals affected with Alzheimer disease (AD) than in the general population and/or healthy controls (Genome Aggregation Database (gnomAD), … (more) This variant is statistically more frequent in individuals affected with Alzheimer disease (AD) than in the general population and/or healthy controls (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)). This is considered a founder variant among individuals of Caribbean Hispanic ancestry (PMID: 11710891, 23114514, 25333068, 27073747). At least one other missense variant at this codon is considered to be pathogenic or likely pathogenic. This variant occurs as the most likely explanation for disease in a significant number of internal cases. Assessment of experimental evidence suggests this variant results in abnormal protein function. Studies show this variant results in increased amyloid-beta 42 peptide production (PMID: 11710891, 12119298, 27930341, 32032730). (less)
Pathogenic (Apr 24, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV002019538.3 First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024
Pathogenic (Jul 30, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Not provided Affected status: unknown Allele origin: germline	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV005414245.1 First in ClinVar: Nov 24, 2024 Last updated: Nov 24, 2024	Publications: PubMed (11) PubMed: 11524469‚ 11710891‚ 18797263‚ 22312439‚ 25333068‚ 26756738‚ 27073747‚ 27312774‚ 27614114‚ 27930341‚ 32032730 Comment: PP3, PM1, PS3, PS4 Number of individuals with the variant: 3
Pathogenic (Nov 14, 2001)	no assertion criteria provided Method: literature only	ALZHEIMER DISEASE, FAMILIAL, 3 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000040071.2 First in ClinVar: Apr 04, 2013 Last updated: May 15, 2017	Publications: PubMed (1) PubMed: 11710891 Comment on evidence: Athan et al. (2001) found that among 206 Caribbean Hispanic families with 2 or more living members with AD, 19 (9.2%) had at least 1 … (more) Athan et al. (2001) found that among 206 Caribbean Hispanic families with 2 or more living members with AD, 19 (9.2%) had at least 1 individual with onset of Alzheimer disease before the age of 55 years (AD3; 607822). In 8 of these 19 families, a gly206-to-ala mutation in the PSEN1 gene was identified. Although not known to be related, all carriers of the G206A mutation tested shared a variant allele at 2 nearby microsatellite polymorphisms, indicating a common ancestor. (less)
Pathogenic (Sep 13, 2024)	no assertion criteria provided Method: clinical testing	PSEN1-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV005358690.1 First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024	Comment: The PSEN1 c.617G>C variant is predicted to result in the amino acid substitution p.Gly206Ala. This variant has been previously documented to be causative for familial … (more) The PSEN1 c.617G>C variant is predicted to result in the amino acid substitution p.Gly206Ala. This variant has been previously documented to be causative for familial Alzheimer’s disease. It was reported to be a common cause of dementia in Hispanics in Puerto Rico and early-onset Alzheimer’s disease in Hispanics in Florida (Arnold et al. 2013. PubMed ID: 23114514; Ravenscroft et al. 2016. PubMed ID: 27073747). This variant is reported in 0.0056% of alleles in individuals of Latino descent in gnomAD. This variant is interpreted as pathogenic. (less)

Comment:

Published functional studies demonstrate a damaging effect resulting in an increase of the amyloid beta ratio (Pimenova et al., 2020); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 22312439, 11710891, 23383383, 22584618, 17522104, 23114514, 25333068, 11524469, 27312774, 27614114, 18797263, 26756738, 23885714, 22475797, 21952501, 20047059, 12119298, 30279455, 27073747, 27930341, 32032730)

Comment:

The PSEN1 c.617G>C; p.Gly206Ala variant (rs63750082) is reported in the literature in several individuals and families affected with early-onset Alzherimer's disease, and is a founder in the Carribean Hispanic population (Athan 2001, Arnold 2013, Lee 2014, Ravenscroft 2016, see link to Alzforum database). This variant is reported in ClinVar (Variation ID: 18143), and is only observed on three alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The glycine at codon 206 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Functional analyses of the variant protein show an impaired ability to properly cleave amyloid precursor protein, which can lead to increased amyloid plaque formation (Athan 2001, Sun 2017). Based on available information, this variant is considered to be pathogenic. References: Link to Alzforum database: https://www.alzforum.org/mutations/psen1-g206a Athan ES et al. A founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families. JAMA. 2001 Nov 14;286(18):2257-63. Arnold SE et al. Frequency and clinicopathological characteristics of presenilin 1 Gly206Ala mutation in Puerto Rican Hispanics with dementia. J Alzheimers Dis. 2013;33(4):1089-95. Lee JH et al. Disease-related mutations among Caribbean Hispanics with familial dementia. Mol Genet Genomic Med. 2014 Sep;2(5):430-7. Ravenscroft TA et al. The presenilin 1 p.Gly206Ala mutation is a frequent cause of early-onset Alzheimer's disease in Hispanics in Florida. Am J Neurodegener Dis. 2016 Mar 1;5(1):94-101. Sun L et al. Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Abeta42 and Abeta40 peptides by gamma-secretase. Proc Natl Acad Sci U S A. 2017 Jan 24;114(4):E476-E485.

Comment:

This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 206 of the PSEN1 protein (p.Gly206Ala). This variant is present in population databases (rs63750082, gnomAD 0.003%). This missense change has been observed in individual(s) with early and late onset Alzheimer disease and Alzheimer disease (PMID: 11524469, 11710891, 18797263, 22312439, 23114514, 25333068, 27073747). It is commonly reported in individuals of Caribbean ancestry (PMID: 11524469, 11710891, 18797263, 22312439, 23114514, 25333068, 27073747). ClinVar contains an entry for this variant (Variation ID: 18143). 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 not expected to disrupt PSEN1 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects PSEN1 function (PMID: 11710891, 27930341). For these reasons, this variant has been classified as Pathogenic.

Comment:

Variant summary: PSEN1 c.617G>C (p.Gly206Ala) 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 allele was found at a frequency of 8e-06 in 251492 control chromosomes. c.617G>C has been reported in the literature in multiple individuals of Caribbean ancestry affected with Alzheimer Disease, Type 3 (Example: Athan_2001). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function indicating an increase in amyloid-beta 42 peptide production (Athan_2001). Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. The following publication have been ascertained in the context of this evaluation (PMID: 11710891). All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

Comment:

This variant is statistically more frequent in individuals affected with Alzheimer disease (AD) than in the general population and/or healthy controls (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)). This is considered a founder variant among individuals of Caribbean Hispanic ancestry (PMID: 11710891, 23114514, 25333068, 27073747). At least one other missense variant at this codon is considered to be pathogenic or likely pathogenic. This variant occurs as the most likely explanation for disease in a significant number of internal cases. Assessment of experimental evidence suggests this variant results in abnormal protein function. Studies show this variant results in increased amyloid-beta 42 peptide production (PMID: 11710891, 12119298, 27930341, 32032730).

Comment:

The PSEN1 c.617G>C variant is predicted to result in the amino acid substitution p.Gly206Ala. This variant has been previously documented to be causative for familial Alzheimer’s disease. It was reported to be a common cause of dementia in Hispanics in Puerto Rico and early-onset Alzheimer’s disease in Hispanics in Florida (Arnold et al. 2013. PubMed ID: 23114514; Ravenscroft et al. 2016. PubMed ID: 27073747). This variant is reported in 0.0056% of alleles in individuals of Latino descent in gnomAD. This variant is interpreted as pathogenic.

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
Novel presenilin 1 and 2 double knock-out cell line for in vitro validation of PSEN1 and PSEN2 mutations.	Pimenova AA	Neurobiology of disease	2020	PMID: 32032730
Historical Migration revealed through a Case of Autosomal Dominant Alzheimer's Disease.	Poblete J	Puerto Rico health sciences journal	2019	PMID: 31536626
Excess Synaptojanin 1 Contributes to Place Cell Dysfunction and Memory Deficits in the Aging Hippocampus in Three Types of Alzheimer's Disease.	Miranda AM	Cell reports	2018	PMID: 29874583
Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease.	Fernández MV	PLoS genetics	2017	PMID: 29091718
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
Next-generation sequencing reveals substantial genetic contribution to dementia with Lewy bodies.	Geiger JT	Neurobiology of disease	2016	PMID: 27312774
The presenilin 1 p.Gly206Ala mutation is a frequent cause of early-onset Alzheimer's disease in Hispanics in Florida.	Ravenscroft TA	American journal of neurodegenerative disease	2016	PMID: 27073747
Neuropathology of Autosomal Dominant Alzheimer Disease in the National Alzheimer Coordinating Center Database.	Ringman JM	Journal of neuropathology and experimental neurology	2016	PMID: 26888304
Loss of stability and hydrophobicity of presenilin 1 mutations causing Alzheimer's disease.	Somavarapu AK	Journal of neurochemistry	2016	PMID: 26756738
Genetic Modifiers of Age at Onset in Carriers of the G206A Mutation in PSEN1 With Familial Alzheimer Disease Among Caribbean Hispanics.	Lee JH	JAMA neurology	2015	PMID: 26214276
Disease-related mutations among Caribbean Hispanics with familial dementia.	Lee JH	Molecular genetics & genomic medicine	2014	PMID: 25333068
Acetylated tau neuropathology in sporadic and hereditary tauopathies.	Irwin DJ	The American journal of pathology	2013	PMID: 23885714
Frequency and clinicopathological characteristics of presenilin 1 Gly206Ala mutation in Puerto Rican Hispanics with dementia.	Arnold SE	Journal of Alzheimer's disease : JAD	2013	PMID: 23114514
C9ORF72 repeat expansions and other FTD gene mutations in a clinical AD patient series from Mayo Clinic.	Wojtas A	American journal of neurodegenerative disease	2012	PMID: 23383383
The French series of autosomal dominant early onset Alzheimer's disease cases: mutation spectrum and cerebrospinal fluid biomarkers.	Wallon D	Journal of Alzheimer's disease : JAD	2012	PMID: 22475797
Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer's disease families.	Cruchaga C	PloS one	2012	PMID: 22312439
Prominent neuroleptic sensitivity in a case of early-onset Alzheimer disease due to presenilin-1 G206A mutation.	Cercy SP	Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology	2008	PMID: 18797263
Presenilin 1 mutations activate gamma 42-secretase but reciprocally inhibit epsilon-secretase cleavage of amyloid precursor protein (APP) and S3-cleavage of notch.	Chen F	The Journal of biological chemistry	2002	PMID: 12119298
A founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families.	Athan ES	JAMA	2001	PMID: 11710891
Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations.	Rogaeva EA	Neurology	2001	PMID: 11524469
click to load more click to collapse

Text-mined citations for rs63750082 ...

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.617G>C (p.Gly206Ala)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs63750082 ...