ClinVar Genomic variation as it relates to human health
NM_000484.4(APP):c.2150T>G (p.Val717Gly)
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_000484.4(APP):c.2150T>G (p.Val717Gly)
Variation ID: 18090 Accession: VCV000018090.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 21q21.3 21: 25891783 (GRCh38) [ NCBI UCSC ] 21: 27264095 (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 Apr 4, 2013 Dec 31, 2022 Oct 27, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000484.4:c.2150T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000475.1:p.Val717Gly missense NM_001136016.3:c.2078T>G NP_001129488.1:p.Val693Gly missense NM_001136129.3:c.1757T>G NP_001129601.1:p.Val586Gly missense NM_001136130.3:c.1982T>G NP_001129602.1:p.Val661Gly missense NM_001136131.3:c.1820T>G NP_001129603.1:p.Val607Gly missense NM_001204301.2:c.2096T>G NP_001191230.1:p.Val699Gly missense NM_001204302.2:c.2039T>G NP_001191231.1:p.Val680Gly missense NM_001204303.2:c.1871T>G NP_001191232.1:p.Val624Gly missense NM_001385253.1:c.1982T>G NP_001372182.1:p.Val661Gly missense NM_201413.3:c.2093T>G NP_958816.1:p.Val698Gly missense NM_201414.3:c.1925T>G NP_958817.1:p.Val642Gly missense NC_000021.9:g.25891783A>C NC_000021.8:g.27264095A>C NG_007376.2:g.284346T>G P05067:p.Val717Gly - Protein change
- V717G, V607G, V699G, V586G, V624G, V642G, V661G, V680G, V693G, V698G
- Other names
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- Canonical SPDI
- NC_000021.9:25891782:A:C
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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
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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
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. |
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APP | No evidence available | Some evidence for dosage pathogenicity |
GRCh38 GRCh37 |
446 | 555 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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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Oct 31, 1991 | RCV000019716.28 | |
Pathogenic (2) |
criteria provided, single submitter
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Oct 27, 2021 | RCV000084576.4 |
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
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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
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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
(Oct 27, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Athena Diagnostics
Accession: SCV002771850.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
Comment:
This variant has not been reported in large, multi-ethnic general populations. (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)) In some published literature, this variant … (more)
This variant has not been reported in large, multi-ethnic general populations. (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)) In some published literature, this variant is referred to as V642G. This variant has been identified in at least one individual with clinical features associated with this gene and appears to be associated with disease in at least one family. At least one other missense variant at this codon is considered to be pathogenic or likely pathogenic. Assessment of experimental evidence suggests this variant results in abnormal protein function. Experiments show this variant results in an increased ratio of amyloid-beta-42 to amyloid-beta-40 (PMID: 7806491, 8886002, 8650548, 20452985). Computational tools predict that this variant is damaging. (less)
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Pathogenic
(Oct 31, 1991)
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no assertion criteria provided
Method: literature only
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ALZHEIMER DISEASE, FAMILIAL, 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000040014.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In affected members of a family with early-onset Alzheimer disease (104300), Chartier-Harlin et al. (1991) identified a 2150T-G transversion in exon 17 of the APP … (more)
In affected members of a family with early-onset Alzheimer disease (104300), Chartier-Harlin et al. (1991) identified a 2150T-G transversion in exon 17 of the APP gene, resulting in a val717-to-glu (V717G) substitution. Average age at onset was 59 years. It was the third mutation identified in codon 717 of the APP gene in families with Alzheimer disease (see V717I, 104760.0002 and V717F, 104760.0003). (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:
not provided
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VIB Department of Molecular Genetics, University of Antwerp
Accession: SCV000116712.1
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_58
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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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Patterns and severity of vascular amyloid in Alzheimer's disease associated with duplications and missense mutations in APP gene, Down syndrome and sporadic Alzheimer's disease. | Mann DMA | Acta neuropathologica | 2018 | PMID: 29770843 |
Clinical phenotype and genetic associations in autosomal dominant familial Alzheimer's disease: a case series. | Ryan NS | The Lancet. Neurology | 2016 | PMID: 27777022 |
Screening exons 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease. | Barber IS | Neurobiology of aging | 2016 | PMID: 26803359 |
Diffusion Kurtosis Imaging: A Possible MRI Biomarker for AD Diagnosis? | Struyfs H | Journal of Alzheimer's disease : JAD | 2015 | PMID: 26444762 |
Genetic influences on atrophy patterns in familial Alzheimer's disease: a comparison of APP and PSEN1 mutations. | Scahill RI | Journal of Alzheimer's disease : JAD | 2013 | PMID: 23380992 |
Structural imaging in early pre-states of dementia. | Smith CD | Biochimica et biophysica acta | 2012 | PMID: 21777674 |
Acceleration of cortical thinning in familial Alzheimer's disease. | Knight WD | Neurobiology of aging | 2011 | PMID: 20005601 |
Aberrant amyloid precursor protein (APP) processing in hereditary forms of Alzheimer disease caused by APP familial Alzheimer disease mutations can be rescued by mutations in the APP GxxxG motif. | Munter LM | The Journal of biological chemistry | 2010 | PMID: 20452985 |
Wild type but not mutant APP is involved in protective adaptive responses against oxidants. | Cenini G | Amino acids | 2010 | PMID: 20063202 |
Relationship between neuronal loss and 'inflammatory plaques' in early onset Alzheimer's disease. | Shepherd CE | Neuropathology and applied neurobiology | 2007 | PMID: 17493013 |
Familial Alzheimer's disease-linked mutations at Val717 of amyloid precursor protein are specific for the increased secretion of A beta 42(43). | Maruyama K | Biochemical and biophysical research communications | 1996 | PMID: 8886002 |
G protein-mediated neuronal DNA fragmentation induced by familial Alzheimer's disease-associated mutants of APP. | Yamatsuji T | Science (New York, N.Y.) | 1996 | PMID: 8650548 |
Predominant deposition of amyloid-beta 42(43) in plaques in cases of Alzheimer's disease and hereditary cerebral hemorrhage associated with mutations in the amyloid precursor protein gene. | Mann DM | The American journal of pathology | 1996 | PMID: 8644866 |
APP717 missense mutation affects the ratio of amyloid beta protein species (A beta 1-42/43 and a beta 1-40) in familial Alzheimer's disease brain. | Tamaoka A | The Journal of biological chemistry | 1994 | PMID: 7806491 |
Familial Alzheimer's disease. A pedigree with a mis-sense mutation in the amyloid precursor protein gene (amyloid precursor protein 717 valine-->glycine). | Kennedy AM | Brain : a journal of neurology | 1993 | PMID: 8461968 |
Pathological changes in the brain of a patient with familial Alzheimer's disease having a missense mutation at codon 717 in the amyloid precursor protein gene. | Mann DM | Neuroscience letters | 1992 | PMID: 1584464 |
Screening for mutations in the open reading frame and promoter of the beta-amyloid precursor protein gene in familial Alzheimer's disease: identification of a further family with APP717 Val-->Ile. | Fidani L | Human molecular genetics | 1992 | PMID: 1303172 |
Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene. | Chartier-Harlin MC | Nature | 1991 | PMID: 1944558 |
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Text-mined citations for rs63749964 ...
HelpRecord last updated May 08, 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.