VCV000441262.3 - ClinVar

NM_000041.3(APOE):c.[434G>A;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.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

This haplotype includes the following variants

NM_000041.3(APOE):c.[434G>A;526C>T]

Other names: APOE, GLY127ASP AND ARG158CYS
Functional consequence: -
Links: ClinGen: CA041311; OMIM: 107741.0009

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.
Hyperlipoproteinemia due to APOE1	Pathogenic (1)	no assertion criteria provided	Apr 1, 1984	RCV000019439.38

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 (Apr 01, 1984)	no assertion criteria provided Method: literature only	HYPERLIPOPROTEINEMIA DUE TO APOE1 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000039729.3 First in ClinVar: Apr 04, 2013 Last updated: Nov 24, 2019	Publications: PubMed (1) PubMed: 6323533 Comment on evidence: Weisgraber et al. (1984) found an electrophoretic variant of apoE in a Finnish hypertriglyceridemic subject. The variant was designated E1 (gly127-to-asp, arg158-to-cys). Family studies showed … (more) Weisgraber et al. (1984) found an electrophoretic variant of apoE in a Finnish hypertriglyceridemic subject. The variant was designated E1 (gly127-to-asp, arg158-to-cys). Family studies showed 'vertical transmission.' The relation of E1 to hypertriglyceridemia was unclear. (less)

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
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
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
Identification of genetic variants associated with response to statin therapy.	Mega JL	Arteriosclerosis, thrombosis, and vascular biology	2009	PMID: 19667110
Pharmacogenetic predictors of statin-mediated low-density lipoprotein cholesterol reduction and dose response.	Voora D	Circulation. Cardiovascular genetics	2008	PMID: 20031551
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
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
Genotyping and sequence analysis of apolipoprotein E isoforms.	Emi M	Genomics	1988	PMID: 3243553
Isolation and characterisation of a variant allele of the gene for human apolipoprotein E.	Gill LL	Biochemical and biophysical research communications	1985	PMID: 2992507
A novel electrophoretic variant of human apolipoprotein E. Identification and characterization of apolipoprotein E1.	Weisgraber KH	The Journal of clinical investigation	1984	PMID: 6323533
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
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_000041.3(APOE):c.[434G>A;526C>T]

Variant Details

NM_000041.3(APOE):c.[434G>A;526C>T]

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...