Mutations

SORL1 E642A

Overview

Clinical Phenotype: Alzheimer's Disease
Position: (GRCh38/hg38):Chr11:121545303 A>C
Position: (GRCh37/hg19):Chr11:121416012 A>C
dbSNP ID: rs776942512
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected Protein Consequence: Missense
Codon Change: GAG to GCG
Reference Isoform: SORL1 Isoform 1 (2214 aa)
Genomic Region: Exon 14

Findings

In a study that included 15,808 Alzheimer’s cases and 16,097 control subjects from multiple European and American cohorts, this allele was observed three times—twice among the AD cases and once among the controls (Holstege et al., 2022).

Previously, the variant was reported in two of 5198 Alzheimer's cases and none of 4491 controls in a dataset from the Alzheimer’s Disease Sequencing Project (ADSP), consisting of subjects of non-Hispanic Caucasian ancestry from whom whole-exome sequencing data were available (Campion et al., 2019). The ADSP contributed data to the 2022 study cited above.

Functional Consequences

The E642A variant was predicted to be tolerated by SIFT, but deleterious by Mutation Taster and PolyPhen-2 (Campion et al., 2019).

Last Updated: 18 Jul 2024

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References

Paper Citations

  1. . Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer's disease. Nat Genet. 2022 Dec;54(12):1786-1794. Epub 2022 Nov 21 PubMed.
  2. . SORL1 genetic variants and Alzheimer disease risk: a literature review and meta-analysis of sequencing data. Acta Neuropathol. 2019 Aug;138(2):173-186. Epub 2019 Mar 25 PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . SORL1 genetic variants and Alzheimer disease risk: a literature review and meta-analysis of sequencing data. Acta Neuropathol. 2019 Aug;138(2):173-186. Epub 2019 Mar 25 PubMed.

Other mutations at this position

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