Mature Protein Numbering: V195E


Clinical Phenotype: Hyperlipoproteinemia Type IIa
Reference Assembly: GRCh37/hg19
Position: Chr19:45412191 T>A
Transcript: NM_000041; ENSG00000130203
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: GTG to GAG
Reference Isoform: APOE Isoform 1
Genomic Region: Exon 4


This variant was identified in a French patient in a cohort of nearly 6,000 unrelated individuals with primary dyslipidemia (Abou Khalil et al., 2022). The carrier had elevated low-density lipoprotein cholesterol (LDL-C) in blood and was diagnosed with autosomal dominant hypercholesterolemia, also known as hyperlipoproteinemia type IIa (HLPP2a). Of note, the carrier was homozygous for a variant in the PCSK9 gene, L21dup, associated with reduced levels of LDL-C. Their APOE genotype was APOE3/E4.

The variant was absent from the gnomAD variant database.

Biological Effect

The biological effect of this variant is unknown, but the authors noted that the proband’s elevated LDL-C levels in the presence of homozygosity for an LDL-C-reducing variant argued for the pathogenicity of V213E. Predictions from multiple computational algorithms, including SIFT, Polyphen2, Mutation Taster, and Provean, were mixed. The variant’s PHRED-scaled CADD score, which integrates diverse information in silico, was 11.3, a score which predicts the variant is in the top 10 percent of the most deleterious substitutions in the human genome. However, it did not reach the commonly used threshold of 20 corresponding to the top 1 percent of the most deleterious substitutions.

Last Updated: 05 Dec 2022


No Available Comments

Make a Comment

To make a comment you must login or register.


Paper Citations

  1. . APOE Molecular Spectrum in a French Cohort with Primary Dyslipidemia. Int J Mol Sci. 2022 May 21;23(10) PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . APOE Molecular Spectrum in a French Cohort with Primary Dyslipidemia. Int J Mol Sci. 2022 May 21;23(10) PubMed.

Disclaimer: Alzforum does not provide medical advice. The Content is for informational, educational, research and reference purposes only and is not intended to substitute for professional medical advice, diagnosis or treatment. Always seek advice from a qualified physician or health care professional about any medical concern, and do not disregard professional medical advice because of anything you may read on Alzforum.