Mutations

APP R468H

Overview

Pathogenicity: Alzheimer's Disease : Uncertain Significance
Clinical Phenotype: None
Reference Assembly: GRCh37/hg19
Position: Chr21:27347438 G>A
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: CGC to CAC
Reference Isoform: APP Isoform APP770 (770 aa)
Genomic Region: Exon 11

Findings

This APP variant was detected in one control case obtained from the KORA-Age cohort, based in Germany (Schulte et al., 2015). Specific information about this individual is not available, but participants in the cohort are described as Caucasian and cognitively healthy at age 65 or older (Schulte et al., 2012).

This variant was also found in the gnomAD at a frequency of 0.00001593 and an allele count of four, with three Finnish and one South Asian carriers (gnomAD v2.1.1, Oct 2021). 

Neuropathology

Not applicable.

Biological Effect

The biological effects of this variant are unknown, but the PHRED-scaled CADD score, which integrates diverse information in silico, was above 20, suggesting a deleterious effect (CADD v.1.6, Oct 2021).

Last Updated: 07 Oct 2021

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References

Paper Citations

  1. Schulte EC, Fukumori A, Mollenhauer B, Hor H, Arzberger T, Perneczky R, Kurz A, Diehl-Schmid J, Hüll M, Lichtner P, Eckstein G, Zimprich A, Haubenberger D, Pirker W, Brücke T, Bereznai B, Molnar MJ, Lorenzo-Betancor O, Pastor P, Peters A, Gieger C, Estivill X, Meitinger T, Kretzschmar HA, Trenkwalder C, Haass C, Winkelmann J. Rare variants in β-Amyloid precursor protein (APP) and Parkinson's disease. Eur J Hum Genet. 2015 Jan 21; PubMed.
  2. Schulte EC, Mollenhauer B, Zimprich A, Bereznai B, Lichtner P, Haubenberger D, Pirker W, Brücke T, Molnar MJ, Peters A, Gieger C, Trenkwalder C, Winkelmann J. Variants in eukaryotic translation initiation factor 4G1 in sporadic Parkinson's disease. Neurogenetics. 2012 Aug;13(3):281-5. Epub 2012 Jun 16 PubMed.

External Citations

  1. gnomAD v2.1.1
  2. CADD v.1.6

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. Schulte EC, Fukumori A, Mollenhauer B, Hor H, Arzberger T, Perneczky R, Kurz A, Diehl-Schmid J, Hüll M, Lichtner P, Eckstein G, Zimprich A, Haubenberger D, Pirker W, Brücke T, Bereznai B, Molnar MJ, Lorenzo-Betancor O, Pastor P, Peters A, Gieger C, Estivill X, Meitinger T, Kretzschmar HA, Trenkwalder C, Haass C, Winkelmann J. Rare variants in β-Amyloid precursor protein (APP) and Parkinson's disease. Eur J Hum Genet. 2015 Jan 21; PubMed.

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