Overview

Clinical Phenotype: Diabetes Mellitus
Position: (GRCh38/hg38):Chr19:44908846 G>-
Position: (GRCh37/hg19):Chr19:45412103 G>-
Transcript: NM_000041; ENSG00000130203
dbSNP ID: NA
Coding/Non-Coding: Coding
DNA Change: Deletion
Expected RNA Consequence: Deletion
Expected Protein Consequence: Frame Shift
Codon Change: GCC to CCC
Reference Isoform: APOE Isoform 1
Genomic Region: Exon 4

Findings

This variant involves the deletion of a guanine that results in a frameshift with a predicted stop codon at position 250. It was identified in a 56-year-old Caucasian from the U.K. with type2 diabetes mellitus (Stephens et al., 2005). The proband’s ApoE protein in blood migrated to the positions of the common ApoE isoforms ApoE3 and R176C (ApoE2). However, DNA sequencing revealed the proband was in fact homozygous for APOE3, but heterozygous for the frameshift mutation. The allele with the mutation, which codes for a smaller protein, likely resulted in the band migrating roughly to the ApoE2 position. Of note, the proband’s ApoE levels in plasma were 70 percent lower than those of APOE3 homozygote controls.

This variant is absent from the gnomAD variant database (v2.1.1, May 2022).

Comments

No Available Comments

Make a Comment

To make a comment you must login or register.

References

Paper Citations

1. Stephens JW, Sozen MM, Whittall RA, Caslake MJ, Bedford D, Acharya J, Hurel SJ, Humphries SE. Three novel mutations in the apolipoprotein E gene in a sample of individuals with type 2 diabetes mellitus. Clin Chem. 2005 Jan;51(1):119-24. Epub 2004 Oct 28 PubMed.

Further Reading

No Available Further Reading