Mutations

PSEN2 I368F

Overview

Pathogenicity: Alzheimer's Disease : Not Classified
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37/hg19
Position: Chr1:227081737 A>T
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: ATC to TTC
Reference Isoform: PSEN2 Isoform 1 (448 aa)
Genomic Region: Exon 12

Findings

This variant was found in a Han Chinese man with Alzheimer’s disease and a family history of dementia (Mao et al., 2021). His age at onset was 60 years. He was homozygous for the APOE3 allele.

This mutation is absent from the gnomAD variant database (v2.1.1, Oct 2021).

Neuropathology
Unknown.

Biological Effect
The biological effect of this variant is unknown, but multiple in silico algorithms (SIFT, PolyPhen2, and LRT) predicted a damaging effect (Mao et al., 2021), and its PHRED-scaled CADD score, which integrates diverse information in silico, was above the commonly used deleteriousness threshold of 20 (CADD v.1.6, Oct 2021). Mao and colleagues classified this as a variant of uncertain significance using the ACMG guidelines (Richards et al., 2015).

Last Updated: 27 Oct 2021

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References

Paper Citations

  1. . Clinical Phenotype and Mutation Spectrum of Alzheimer's Disease with Causative Genetic Mutation in a Chinese Cohort. Curr Alzheimer Res. 2021;18(3):265-272. PubMed.
  2. . Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-24. Epub 2015 Mar 5 PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Clinical Phenotype and Mutation Spectrum of Alzheimer's Disease with Causative Genetic Mutation in a Chinese Cohort. Curr Alzheimer Res. 2021;18(3):265-272. PubMed.

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