Familial hypercholesterolaemia

Gene: APOE

Green List (high evidence)

APOE (apolipoprotein E)
EnsemblGeneIds (GRCh38): ENSG00000130203
EnsemblGeneIds (GRCh37): ENSG00000130203
OMIM: 107741, Gene2Phenotype
APOE is in 10 panels

5 reviews

Sarah Leigh (Genomics England Curator)

Comment on phenotypes: Including hypercholesterolaemia
Created: 2 Jul 2019, 1:19 p.m. | Last Modified: 2 Jul 2019, 1:19 p.m.
Panel Version: 1.24

Simon Thomas (Wessex)

Green List (high evidence)

The APOE (NM_00041) in-frame deletion c.500_502del p.(Leu167del) has been identified in four singletons recruited to the 100KGP for FH analysis by the Wessex GMC.
Created: 18 Feb 2019, 5:43 p.m.

Helen Brittain (Genomics England Curator)

Green List (high evidence)

Comment on list classification: See comments under 9th November 2017 review
Created: 9 Nov 2017, 9:32 a.m.
At a meeting on 7/11/17 with Prof Steve Humphries and Dr. Ellen Thomas we discussed this. There is sufficient evidence for inclusion; 4 unrelated cases (inc one large family) with hypercholesterolaemia (see above PMIDs). Considered appropriate for inclusion. Please note that the homozygous APOE4 allele (presence of Arg at 112 and 156) that is associated with an increased risk of Alzheimer's would not be expected to be tiered via this panel in view of allele frequency and the combination of two variants in a homozygous state.
Created: 9 Nov 2017, 9:31 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Autosomal dominant hypercholesterolaemia

Publications

Ellen McDonagh (Genomics England Curator)

On the Inherited Cardiac Condition Genes panel for Familial Hypercholesterolaemia reported in: Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes, Pua et al, Journal of Cardiovascular Translational Research, online Feb 2016 (doi:10.​1007/​s12265-016-9673-5). The panel contains disease-causing, putatively pathogenic, research and phenocopy genes, and it is unclear from the publication whether this gene falls into the disease-causing category. No. of mutations indicated in supplemental table = 1.
Created: 19 Feb 2016, 2:47 p.m.

Ellen Thomas (Genomics England)

Red List (low evidence)

One haplotype is associated with hypercholesterolaemia in a small proportion of homozygotes, but most homozygotes have normal cholesterol. Homozygosity for another haplotype causes increased risk for Alzheimers disease. We don't want to know about the Alzheimers risk, and the hypercholesterolaemia risk is not clinically useful information, so this gene should NOT be on the panel for FH.
Created: 13 Dec 2015, 9:43 p.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • Eligibility statement prior genetic testing
Phenotypes
  • Hyperlipoproteinemia, type III 617347
OMIM
107741
Clinvar variants
Variants in APOE
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

2 Jul 2019, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: APOE were changed from Autosomal dominant hypercholesterolaemia to Hyperlipoproteinemia, type III 617347

1 Jul 2019, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: APOE were set to PMID: 23433584; 22949395; 26802169

9 Nov 2017, Gel status: 3

Set Phenotypes

Helen Brittain (Genomics England Curator)

Phenotypes for APOE were set to Autosomal dominant hypercholesterolaemia

9 Nov 2017, Gel status: 3

Set publications

Helen Brittain (Genomics England Curator)

Publications for APOE were set to PMID: 23433584; 22949395; 26802169

9 Nov 2017, Gel status: 3

Set mode of inheritance

Helen Brittain (Genomics England Curator)

Mode of inheritance for APOE was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

9 Nov 2017, Gel status: 3

Gene classified by Genomics England curator

Helen Brittain (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

28 Jun 2016, Gel status: 1

Gene classified by Genomics England curator

Ellen Thomas (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

28 Jun 2016, Gel status: 1

Gene classified by Genomics England curator

Ellen Thomas (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

7 Oct 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

APOE was added to Familial hypercholesterolaemiapanel. Source: Emory Genetics Laboratory

7 Oct 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

APOE was added to Familial hypercholesterolaemiapanel. Source: Radboud University Medical Center, Nijmegen

7 Oct 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

APOE was added to Familial hypercholesterolaemiapanel. Source: Radboud University Medical Center, Nijmegen

7 Oct 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

APOE was added to Familial hypercholesterolaemiapanel. Sources: Eligibility statement prior genetic testing