Mutations

APP E599K

Overview

Pathogenicity: Alzheimer's Disease : Not Pathogenic
Clinical Phenotype: None, Parkinson's Disease, Parkinson's Disease Dementia
Reference Assembly: GRCh37 (105)
Position: Chr21:27284167 G>A
dbSNP ID: rs140304729
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: GAA to AAA
Reference Isoform: APP Isoform APP770 (770 aa)
Genomic Region: Exon 14

Findings

This variant in APP was found in an exome-sequencing study of 141 individuals with late-onset Alzheimer’s disease and 179 elderly controls without neuropathology. The variant was detected in one Caucasian control who was at least 60 years of age at death. APOE genotype was E3/E4. Further clinical details were not available (Sassi et al., 2014).

This variant was also detected in one out of 188 cases with Parkinson’s disease, two out of 188 cases with PD with dementia, and one out of 376 controls (Schulte et al., 2015).

The E599K variant was also detected by whole-exome sequencing in two of 424 French people with early onset AD. Clinical details were not reported (Nicolas et al., 2015).

Neuropathology

Not applicable.

Biological Effect

Unknown. In silico, this variant is predicted to be possibly damaging. It is classified as a benign polymorphism according to the algorithm proposed by Guerreiro et al., 2010 (Sassi et al., 2014).

Last Updated: 02 Oct 2015

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References

Paper Citations

  1. . Investigating the role of rare coding variability in Mendelian dementia genes (APP, PSEN1, PSEN2, GRN, MAPT, and PRNP) in late-onset Alzheimer's disease. Neurobiol Aging. 2014 Dec;35(12):2881.e1-6. Epub 2014 Jun 16 PubMed.
  2. . Rare variants in β-Amyloid precursor protein (APP) and Parkinson's disease. Eur J Hum Genet. 2015 Jan 21; PubMed.
  3. . Screening of dementia genes by whole-exome sequencing in early-onset Alzheimer disease: input and lessons. Eur J Hum Genet. 2015 Aug 5; PubMed.
  4. . Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP. Neurobiol Aging. 2010 May;31(5):725-31. Epub 2008 Jul 30 PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Investigating the role of rare coding variability in Mendelian dementia genes (APP, PSEN1, PSEN2, GRN, MAPT, and PRNP) in late-onset Alzheimer's disease. Neurobiol Aging. 2014 Dec;35(12):2881.e1-6. Epub 2014 Jun 16 PubMed.

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