Mutations

APP T719N

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37 (105)
Position: Chr21:27264089 C>A
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: ACC to AAC
Reference Isoform: APP Isoform APP770 (770 aa)
Genomic Region: Exon 17

Findings

This mutation was first identified in a subject with a family history of autosomal-dominant Alzheimer’s disease (Scahill et al., 2013). This carrier was reported to have a “typical clinical presentation for FAD, with impairment of episodic memory progressing to global cognitive decline from [the] mid-late 40s.” The mutation was absent from 100 healthy, unrelated Caucasian control subjects.

Subsequently, the mutation was found in a subject enrolled in the Dominantly Inherited Alzheimer Network (DIAN) (Hsu et al., 2018). The proband became symptomatic at 45 years of age, the same age at which his or her parent was diagnosed with AD. The mutation was absent from the Exon Variant Server and ExAC databases.

This mutation was classified as probably pathogenic according to the algorithm employed by the DIAN Expanded Registry (Hsu et al., 2018).

Neuropathology

Unknown.

Biological Effect

In a heterologous expression system, the T719N mutation led to increased levels of Aβ42 and an elevated Aβ42:Aβ40 ratio, compared with wild-type APP (Hsu et al., 2018).

Last Updated: 19 Jun 2019

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References

Paper Citations

  1. . Genetic Influences on Atrophy Patterns in Familial Alzheimer's Disease: A Comparison of APP and PSEN1 Mutations. J Alzheimers Dis. 2013 Jan 1;35(1):199-212. PubMed.
  2. . Discovery and validation of autosomal dominant Alzheimer's disease mutations. Alzheimers Res Ther. 2018 Jul 18;10(1):67. PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Discovery and validation of autosomal dominant Alzheimer's disease mutations. Alzheimers Res Ther. 2018 Jul 18;10(1):67. PubMed.

Other mutations at this position

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