Mutations

PSEN1 T122A

Overview

Pathogenicity: Frontotemporal Dementia : Not Classified
Clinical Phenotype: Frontotemporal Dementia
Reference Assembly: GRCh37/hg19
Position: Chr14:73640299 A>G
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: ACC to GCC
Reference Isoform: PSEN1 Isoform 1 (467 aa)
Genomic Region: Exon 5

Findings

This mutation was found in a U.K. genetic screen of more than 3,000 samples of patients with dementia (Koriath et al., 2018). The mutation carrier was a man diagnosed with frontotemporal dementia whose symptoms emerged at age 55. One known relative had late-onset dementia. The mutation was absent from genetic variant databases, including ExAC and gnomAD.

Neuropathology
Unknown

Biological Effect
The biological effect of this mutation is unknown. It involves a substitution of a polar amino acid with a hydrophobic one in the first luminal region of PSEN1, adjacent to a site with a probably pathogenic mutation. Based on their proposed pathogenicity algorithm, Koriath and colleagues classified the mutation as likely deleterious.

Several in silico algorithms (SIFT, Polyphen-2, LRT, MutationTaster, MutationAssessor, FATHMM, PROVEAN, CADD, REVEL, and Reve in the VarCards database) predicted this variant is damaging (Xiao et al., 2021).

Last Updated: 08 Sep 2021

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References

Paper Citations

  1. . Predictors for a dementia gene mutation based on gene-panel next-generation sequencing of a large dementia referral series. Mol Psychiatry. 2018 Oct 2; PubMed.
  2. . APP, PSEN1, and PSEN2 Variants in Alzheimer's Disease: Systematic Re-evaluation According to ACMG Guidelines. Front Aging Neurosci. 2021;13:695808. Epub 2021 Jun 18 PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Predictors for a dementia gene mutation based on gene-panel next-generation sequencing of a large dementia referral series. Mol Psychiatry. 2018 Oct 2; PubMed.

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