Mutations

APP A713V

Overview

Pathogenicity: Alzheimer's Disease : Not Pathogenic
Clinical Phenotype: None
Reference Assembly: GRCh37 (105)
Position: Chr21:27264107 C>T
dbSNP ID: rs1800557
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: GCG to GTG
Reference Isoform: APP Isoform APP770 (770 aa)
Genomic Region: Exon 17

Findings

This variant was originally described in an individual with schizophrenia and cognitive deficits (Jones et al., 1992), raising the possibility of pathogenicity. Subsequent studies did not support a pathogenic role for this variant in either schizophrenia or Alzheimer's disease. The variant was not associated with schizophrenia in a study of 191 individuals in 24 families (Mant et al., 1992), and in a study of 98 AD cases and 56 elderly healthy controls, it was found only in a control (Forsell et al., 1995). The variant has been reported in eight individuals of European ancestry, with a global frequency of 0.00006592 in the ExAC variant database (ExAc v1.0, Sep 2020).

Neuropathology

Not applicable.

Biological Effect

Mouse neuroblastoma cells expressing this variant secreted less than half the amount of both Aβ42 and Aβ40 compared with cells expressing wild-type PSEN1. The Aβ42/Aβ40 ratio was similar to controls (Hsu et al., 2020). In silico analyses predicted this mutation is probably damaging (PolyPhen) and deleterious (SIFT). Hsu et al. classified the mutation as not pathogenic and possibly protective.

Last Updated: 01 Sep 2020

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References

Paper Citations

  1. . Mutation in codon 713 of the beta amyloid precursor protein gene presenting with schizophrenia. Nat Genet. 1992 Jul;1(4):306-9. PubMed.
  2. . Schizophrenia scepticism. Nat Genet. 1992 Sep;2(1):12. PubMed.
  3. . Amyloid precursor protein mutation at codon 713 (Ala-->Val) does not cause schizophrenia: non-pathogenic variant found at codon 705 (silent). Neurosci Lett. 1995 Jan 23;184(2):90-3. PubMed.
  4. . Systematic validation of variants of unknown significance in APP, PSEN1 and PSEN2. Neurobiol Dis. 2020 Jun;139:104817. Epub 2020 Feb 19 PubMed.

External Citations

  1. ExAc v1.0

Further Reading

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database

Protein Diagram

Primary Papers

  1. . Mutation in codon 713 of the beta amyloid precursor protein gene presenting with schizophrenia. Nat Genet. 1992 Jul;1(4):306-9. PubMed.

Other mutations at this position

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