ClinVar Genomic variation as it relates to human health
NM_000021.4(PSEN1):c.856C>G (p.Leu286Val)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000021.4(PSEN1):c.856C>G (p.Leu286Val)
Variation ID: 18126 Accession: VCV000018126.23
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 14q24.2 14: 73198117 (GRCh38) [ NCBI UCSC ] 14: 73664825 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Feb 20, 2014 May 12, 2024 Jun 1, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000021.4:c.856C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000012.1:p.Leu286Val missense NM_007318.3:c.844C>G NP_015557.2:p.Leu282Val missense NC_000014.9:g.73198117C>G NC_000014.8:g.73664825C>G NG_007386.2:g.66647C>G LRG_224:g.66647C>G LRG_224t1:c.856C>G LRG_224p1:p.Leu286Val P49768:p.Leu286Val - Protein change
- L286V, L282V
- Other names
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- Canonical SPDI
- NC_000014.9:73198116:C:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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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 | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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. |
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PSEN1 | - | - |
GRCh38 GRCh37 |
514 | 531 |
Conditions - Germline
Condition
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
no assertion criteria provided
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Jun 29, 1995 | RCV000019754.29 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jun 1, 2021 | RCV000084387.20 |
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
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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. |
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Pathogenic
(Jul 21, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Athena Diagnostics
Accession: SCV000614830.1
First in ClinVar: Feb 20, 2014 Last updated: Feb 20, 2014 |
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Pathogenic
(Jun 01, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001248749.21
First in ClinVar: May 12, 2020 Last updated: May 12, 2024 |
Number of individuals with the variant: 3
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Pathogenic
(Jun 29, 1995)
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no assertion criteria provided
Method: literature only
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ALZHEIMER DISEASE, FAMILIAL, 3
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000040052.2
First in ClinVar: Apr 04, 2013 Last updated: May 15, 2017 |
Comment on evidence:
In a pedigree with chromosome 14-linked early-onset Alzheimer disease (AD3; 607822), Sherrington et al. (1995) identified a mutation in the PSEN1 gene, resulting in a … (more)
In a pedigree with chromosome 14-linked early-onset Alzheimer disease (AD3; 607822), Sherrington et al. (1995) identified a mutation in the PSEN1 gene, resulting in a leu286-to-val (L286V) substitution. (less)
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not provided
(-)
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no classification provided
Method: not provided
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not provided
Affected status: not provided
Allele origin:
unknown
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VIB Department of Molecular Genetics, University of Antwerp
Accession: SCV000116523.1
First in ClinVar: Feb 20, 2014 Last updated: Feb 20, 2014
Comment:
http://phencode.bx.psu.edu/cgi-bin/phencode/phencode?build=hg18&id=ADM_43
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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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 |
Presenilin 1 mutations influence processing and trafficking of the ApoE receptor apoER2. | Wang W | Neurobiology of aging | 2017 | PMID: 27810638 |
Expression of familial Alzheimer disease presenilin 1 gene attenuates vesicle traffic and reduces peptide secretion in cultured astrocytes devoid of pathologic tissue environment. | Stenovec M | Glia | 2016 | PMID: 26462451 |
Alzheimer presenilin-1 mutations dramatically reduce trimming of long amyloid β-peptides (Aβ) by γ-secretase to increase 42-to-40-residue Aβ. | Fernandez MA | The Journal of biological chemistry | 2014 | PMID: 25239621 |
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 |
Dissociation between the processivity and total activity of γ-secretase: implications for the mechanism of Alzheimer's disease-causing presenilin mutations. | Quintero-Monzon O | Biochemistry | 2011 | PMID: 21919498 |
Presenilin 1 mutants impair the self-renewal and differentiation of adult murine subventricular zone-neuronal progenitors via cell-autonomous mechanisms involving notch signaling. | Veeraraghavalu K | The Journal of neuroscience : the official journal of the Society for Neuroscience | 2010 | PMID: 20484632 |
Mutational analysis in early-onset familial dementia in the Japanese population. The role of PSEN1 and MAPT R406W mutations. | Ikeuchi T | Dementia and geriatric cognitive disorders | 2008 | PMID: 18587238 |
Presenilin-1 regulates the neuronal threshold to excitotoxicity both physiologically and pathologically. | Grilli M | Proceedings of the National Academy of Sciences of the United States of America | 2000 | PMID: 11070093 |
Separation of presenilin function in amyloid beta-peptide generation and endoproteolysis of Notch. | Kulic L | Proceedings of the National Academy of Sciences of the United States of America | 2000 | PMID: 10811883 |
Presenilin-1 mutations increase levels of ryanodine receptors and calcium release in PC12 cells and cortical neurons. | Chan SL | The Journal of biological chemistry | 2000 | PMID: 10764737 |
Presenilin 1 controls gamma-secretase processing of amyloid precursor protein in pre-golgi compartments of hippocampal neurons. | Annaert WG | The Journal of cell biology | 1999 | PMID: 10525535 |
Enhancement of amyloid beta 42 secretion by 28 different presenilin 1 mutations of familial Alzheimer's disease. | Murayama O | Neuroscience letters | 1999 | PMID: 10327206 |
Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice. | Citron M | Nature medicine | 1997 | PMID: 8986743 |
Alzheimer's PS-1 mutation perturbs calcium homeostasis and sensitizes PC12 cells to death induced by amyloid beta-peptide. | Guo Q | Neuroreport | 1996 | PMID: 9051814 |
Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. | Sherrington R | Nature | 1995 | PMID: 7596406 |
Familial Alzheimer disease: a large, multigeneration German kindred. | Frommelt P | Alzheimer disease and associated disorders | 1991 | PMID: 2025423 |
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Text-mined citations for rs63751235 ...
HelpRecord last updated May 12, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.