Mutations

PSEN1 G371C

Overview

Pathogenicity: Alzheimer's Disease : Not Classified
Clinical Phenotype: Alzheimer's Disease
Reference Assembly: GRCh37/hg19
Position: Chr14:73678632 G>T
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: GGT to TGT
Reference Isoform: PSEN1 Isoform 1 (467 aa)
Genomic Region: Exon 10

Findings

This variant was found in one individual in a study that screened the APP, PSEN1, and PSEN2 genes in 1,431 Alzheimer’s disease (AD) patients from the Belgian neurology consortium BELNEU (Perrone et al., 2020). The authors used a targeted re-sequencing gene-panel and selected non-synonymous variants with a less than one percent minor allele frequency.

The proband’s APOE genotype was APOE3/4. The variant is absent from both the gnomAD and ExAC variant databases.

Neuropathology 

Unknown

Biological Effect

The biological effect of this mutation is unknown. 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: 13 Sep 2021

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References

Paper Citations

  1. Perrone F, Bjerke M, Hens E, Sieben A, Timmers M, De Roeck A, Vandenberghe R, Sleegers K, Martin JJ, De Deyn PP, Engelborghs S, van der Zee J, Van Broeckhoven C, Cacace R, BELNEU Consortium. Amyloid-β1-43 cerebrospinal fluid levels and the interpretation of APP, PSEN1 and PSEN2 mutations. Alzheimers Res Ther. 2020 Sep 11;12(1):108. PubMed.
  2. Xiao X, Liu H, Liu X, Zhang W, Zhang S, Jiao B. 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. Perrone F, Bjerke M, Hens E, Sieben A, Timmers M, De Roeck A, Vandenberghe R, Sleegers K, Martin JJ, De Deyn PP, Engelborghs S, van der Zee J, Van Broeckhoven C, Cacace R, BELNEU Consortium. Amyloid-β1-43 cerebrospinal fluid levels and the interpretation of APP, PSEN1 and PSEN2 mutations. Alzheimers Res Ther. 2020 Sep 11;12(1):108. PubMed.

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