Mutations

PSEN1 N39Y

Overview

Pathogenicity: Alzheimer's Disease : Not Classified
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37/hg19
Position: Chr14:73637532 A>T
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: AAC to TAC
Reference Isoform: PSEN1 Isoform 1 (467 aa)
Genomic Region: Exon 4

Findings

This mutation was identified in a genetic screen of 757 patients in the U.K. with early onset Alzheimer’s disease (Koriath et al., 2018). It was reported as also present in the gnomAD variant database with an allele count of one and a frequency of 0.000004.  Koriath et al. described the variant as most likely fully penetrant (95% CI > 100% penetrance), and classified it as possibly deleterious following the ACMG-AMP guidelines (Richards et al., 2015).

Biological Finding

In silico algorithms to predict the effects of this variant 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).

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. . 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.
  3. . 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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