Mutations

PSEN1 S365Y

Overview

Pathogenicity: Alzheimer's Disease : Not Classified
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37/hg19
Position: Chr14:73678615 C>A
dbSNP ID: rs63750941
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: TCC to TAC
Reference Isoform: PSEN1 Isoform 1 (467 aa)
Genomic Region: Exon 10

Findings

The S365Y mutation was found in one individual with Alzheimer's disease. Further details were not provided, except that it was co-inherited with a second PSEN1 mutation M146V, which has been classified as pathogenic (Rogaeva et al., 2001). S365Y was absent from the gnomAD variant database (gnomAD v2.1.1, August 2021).

Neuropathology

Unknown.

Biological Effect

The biological effect of this variant is unknown. In silico algorithms to predict its effects on protein function (SIFT, Polyphen-2, LRT, MutationTaster, MutationAssessor, FATHMM, PROVEAN, CADD, REVEL, and Reve in the VarCards database) yielded conflicting results (Xiao et al., 2021), but the CADD-PHRED tool, which integrates diverse information, gave it a high deleteriousness score above 20 (CADD v.1.6, Sep 2021).

Last Updated: 22 Sep 2021

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References

Paper Citations

  1. . Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations. Neurology. 2001 Aug 28;57(4):621-5. 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.

Other Citations

External Citations

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

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations. Neurology. 2001 Aug 28;57(4):621-5. PubMed.

Other mutations at this position

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