Overview

Pathogenicity: Amyotrophic Lateral Sclerosis : Not Classified
Clinical Phenotype: Amyotrophic Lateral Sclerosis
Position: (GRCh38/hg38):Chr14:73192704 G>C
Position: (GRCh37/hg19):Chr14:73659412 G>C
dbSNP ID: rs1384308168
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: TGG to TGC
Reference Isoform: PSEN1 Isoform 1 (467 aa)
Genomic Region: Exon 7

Findings

This mutation was found in a targeted sequencing screen of 169 genes in 242 patients with amyotrophic lateral sclerosis (ALS) from the Coriell collection of North American Caucasian DNA samples (Couthouis et al., 2014). The carrier was a man diagnosed with bulbar-onset ALS and no known family history of the disease. He was 61 years old at the time of sample collection. The mutation was absent from the ESP6500, 1000genomes, and dbSNPv137 databases.

Neuropathology
Unknown.

Biological Effect
The biological effect of this mutation is unknown. According to the PhyloP algorithm, the codon is evolutionarily conserved. 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 (Couthouis et al., 2014; Xiao et al., 2021).

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References

Paper Citations

1. Couthouis J, Raphael AR, Daneshjou R, Gitler AD. Targeted exon capture and sequencing in sporadic amyotrophic lateral sclerosis. PLoS Genet. 2014 Oct;10(10):e1004704. Epub 2014 Oct 9 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