VCV000666796.5 - ClinVar

NM_000041.2:c.[388T>C];[526C>T]

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.

(1)

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.

Uncertain significance

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

This genotype includes the following variants

NM_000041.2:c.[388T>C];[526C>T]

Other names: p.[Cys130Arg]
[Arg176Cys]
Functional consequence: -
Links: -

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.
APOE		-	-	GRCh38 GRCh37	190	209

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.
not specified	Uncertain significance (1)	criteria provided, single submitter	Jan 18, 2019	RCV000825286.13

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.
Uncertain significance (Jan 18, 2019)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000966580.1 First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019	Publications: PubMed (3) PubMed: 27260402‚ 9343467‚ 23571587 Comment: proposed classification - variant undergoing re-assessment, contact laboratory Number of individuals with the variant: 2

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

Title	Author	Journal	Year	Link
APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline.	Montagne A	Nature	2020	PMID: 32376954
APOB gene polymorphisms may affect the risk of minor or minimal bleeding complications in patients on warfarin maintaining therapeutic INR.	Yee J	European journal of human genetics : EJHG	2019	PMID: 31186542
Increased yield of full GBA sequencing in Ashkenazi Jews with Parkinson's disease.	Ruskey JA	European journal of medical genetics	2019	PMID: 29842932
Differential burden of rare protein truncating variants in Alzheimer's disease patients compared to centenarians.	Freudenberg-Hua Y	Human molecular genetics	2016	PMID: 27260402
Differential burden of rare protein truncating variants in Alzheimer's disease patients compared to centenarians.	Freudenberg-Hua Y	Human molecular genetics	2016	PMID: 27260402
Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4,and the risk of late-onset Alzheimer disease in African Americans.	Reitz C	JAMA	2013	PMID: 23571587
Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4,and the risk of late-onset Alzheimer disease in African Americans.	Reitz C	JAMA	2013	PMID: 23571587
Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy.	Liu CC	Nature reviews. Neurology	2013	PMID: 23296339
APOE4-specific changes in Aβ accumulation in a new transgenic mouse model of Alzheimer disease.	Youmans KL	The Journal of biological chemistry	2012	PMID: 23060451
Association between apolipoprotein E gene polymorphism and the risk of vascular dementia: a meta-analysis.	Yin YW	Neuroscience letters	2012	PMID: 22381401
Aggregation of α-synuclein in brain samples from subjects with glucocerebrosidase mutations.	Choi JH	Molecular genetics and metabolism	2011	PMID: 21742527
Comprehensive whole-genome and candidate gene analysis for response to statin therapy in the Treating to New Targets (TNT) cohort.	Thompson JF	Circulation. Cardiovascular genetics	2009	PMID: 20031582
Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease.	Sidransky E	The New England journal of medicine	2009	PMID: 19846850
Identification of genetic variants associated with response to statin therapy.	Mega JL	Arteriosclerosis, thrombosis, and vascular biology	2009	PMID: 19667110
Longitudinal modeling of age-related memory decline and the APOE epsilon4 effect.	Caselli RJ	The New England journal of medicine	2009	PMID: 19605830
Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset.	Nichols WC	Neurology	2009	PMID: 18987351
Pharmacogenetic predictors of statin-mediated low-density lipoprotein cholesterol reduction and dose response.	Voora D	Circulation. Cardiovascular genetics	2008	PMID: 20031551
Phenotypic heterogeneity of N370S homozygotes with type I Gaucher disease: an analysis of 798 patients from the ICGG Gaucher Registry.	Fairley C	Journal of inherited metabolic disease	2008	PMID: 18979180
Gaucher disease: mutation and polymorphism spectrum in the glucocerebrosidase gene (GBA).	Hruska KS	Human mutation	2008	PMID: 18338393
Tolerability of statins is not linked to CYP450 polymorphisms, but reduced CYP2D6 metabolism improves cholesteraemic response to simvastatin and fluvastatin.	Zuccaro P	Pharmacological research	2007	PMID: 17289397
Polymorphisms in the apolipoprotein A5 (APOA5) gene and type III hyperlipidemia.	Evans D	Clinical genetics	2005	PMID: 16143024
An association study of 43 SNPs in 16 candidate genes with atorvastatin response.	Thompson JF	The pharmacogenomics journal	2005	PMID: 16103896
APOE genotype and cognitive decline in a middle-aged cohort.	Blair CK	Neurology	2005	PMID: 15668424
Impact of APOE in mild cognitive impairment.	Farlow MR	Neurology	2004	PMID: 15557508
APOE-epsilon4 predicts dementia but not other psychiatric disorders after traumatic brain injury.	Koponen S	Neurology	2004	PMID: 15326261
Longitudinal changes in cognition and behavior in asymptomatic carriers of the APOE e4 allele.	Caselli RJ	Neurology	2004	PMID: 15184602
Functional analysis of 13 GBA mutant alleles identified in Gaucher disease patients: Pathogenic changes and "modifier" polymorphisms.	Montfort M	Human mutation	2004	PMID: 15146461
Accelerated evolution of brain atrophy and "black holes" in MS patients with APOE-epsilon 4.	Enzinger C	Annals of neurology	2004	PMID: 15048896
ApoE and clusterin cooperatively suppress Abeta levels and deposition: evidence that ApoE regulates extracellular Abeta metabolism in vivo.	DeMattos RB	Neuron	2004	PMID: 14741101
APOE genotype influences acquisition and recall following traumatic brain injury.	Crawford FC	Neurology	2002	PMID: 11940706
Apolipoprotein E epsilon 4 and short-term recovery from predominantly mild brain injury.	Liberman JN	Neurology	2002	PMID: 11940689
Accelerated hippocampal atrophy in Alzheimer's disease with apolipoprotein E epsilon4 allele.	Mori E	Annals of neurology	2002	PMID: 11835377
Dominant negative effects of apolipoprotein E4 revealed in transgenic models of neurodegenerative disease.	Buttini M	Neuroscience	2000	PMID: 10799751
Apolipoprotein E-epsilon4 genotype predicts a poor outcome in survivors of traumatic brain injury.	Friedman G	Neurology	1999	PMID: 9932938
Type III hyperlipoproteinemia and spontaneous atherosclerosis in mice resulting from gene replacement of mouse Apoe with human Apoe*2.	Sullivan PM	The Journal of clinical investigation	1998	PMID: 9649566
Association of apolipoprotein E polymorphism with outcome after head injury.	Teasdale GM	Lancet (London, England)	1997	PMID: 10213549
Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium.	Farrer LA	JAMA	1997	PMID: 9343467
Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium.	Farrer LA	JAMA	1997	PMID: 9343467
Relative risk of Alzheimer disease and age-at-onset distributions, based on APOE genotypes among elderly African Americans, Caucasians, and Hispanics in New York City.	Tang MX	American journal of human genetics	1996	PMID: 8644717
Apolipoprotein E epsilon4 association with dementia in a population-based study: The Framingham study.	Myers RH	Neurology	1996	PMID: 8618665
Analysis of human acid beta-glucosidase by site-directed mutagenesis and heterologous expression.	Grace ME	The Journal of biological chemistry	1994	PMID: 8294487
Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease.	Saunders AM	Neurology	1993	PMID: 8350998
Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.	Corder EH	Science (New York, N.Y.)	1993	PMID: 8346443
Genetic heterogeneity in type 1 Gaucher disease: multiple genotypes in Ashkenazic and non-Ashkenazic individuals.	Tsuji S	Proceedings of the National Academy of Sciences of the United States of America	1988	PMID: 3353383
Genotyping and sequence analysis of apolipoprotein E isoforms.	Emi M	Genomics	1988	PMID: 3243553
Isolation, characterization, and mapping to chromosome 19 of the human apolipoprotein E gene.	Das HK	The Journal of biological chemistry	1985	PMID: 3922972
Isolation and characterisation of a variant allele of the gene for human apolipoprotein E.	Gill LL	Biochemical and biophysical research communications	1985	PMID: 2992507
Nucleotide sequence and structure of the human apolipoprotein E gene.	Paik YK	Proceedings of the National Academy of Sciences of the United States of America	1985	PMID: 2987927
Identical structural and receptor binding defects in apolipoprotein E2 in hypo-, normo-, and hypercholesterolemic dysbetalipoproteinemia.	Rall SC Jr	The Journal of clinical investigation	1983	PMID: 6300187
Human E apoprotein heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo-E isoforms.	Weisgraber KH	The Journal of biological chemistry	1981	PMID: 7263700
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=APOE	-	-	-	-
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=APOE	-	-	-	-
https://www.pharmgkb.org/clinicalAnnotation/1183492249	-	-	-	-
https://www.pharmgkb.org/variant/PA166155341	-	-	-	-
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Text-mined citations for this variant ...

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_000041.2:c.[388T>C];[526C>T]

Variant Details

NM_000041.2:c.[388T>C];[526C>T]

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...