Overview

Clinical Phenotype: Alzheimer's Disease
Position: (GRCh38/hg38):Chr11:121497030 T>G
Position: (GRCh37/hg19):Chr11:121367739 T>G
dbSNP ID: NA
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected Protein Consequence: Missense
Codon Change: ATG to AGG
Reference Isoform: SORL1 Isoform 1 (2214 aa)
Genomic Region: Exon 6

Findings

In a study that included 18,959 Alzheimer’s cases and 21,893 control subjects from multiple European and American cohorts, this allele was observed once among the AD cases (Henne Holstege, personal communication).

Functional Consequences

Methionine-307 is part of a stretch of hydrophobic residues that is conserved among the blades of the VPS10P β-propeller. These hydrophobic motifs are thought to have a role in stabilizing the β-propeller. Andersen and colleagues have predicted that non-conservative substitutions at this position will have a moderate effect on disease-risk (Andersen et al., 2023).

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References

Paper Citations

1. Andersen OM, Monti G, Jensen AM, deWaal M, Hulsman M, Olsen JG, Holstege H. Relying on the relationship with known disease-causing variants in homologous proteins to predict pathogenicity of SORL1 variants in Alzheimer's disease. 2023 Feb 27 10.1101/2023.02.27.524103 (version 1) bioRxiv.

Further Reading

No Available Further Reading