Mutations
SORL1 D1620V
Overview
Clinical
Phenotype: Alzheimer's Disease
Position: (GRCh38/hg38):Chr11:121605482 A>T
Position: (GRCh37/hg19):Chr11:121476191 A>T
dbSNP ID: NA
Coding/Non-Coding: Coding
DNA
Change: Substitution
Expected Protein
Consequence: Missense
Codon
Change: GAT to GTT
Reference
Isoform: SORL1 Isoform 1 (2214 aa)
Genomic
Region: Exon 35
Findings
In a Dutch sample of 640 Alzheimer’s disease cases and 1268 controls, a 97-year-old control subject was found to be a heterozygous carrier of this variant (Holstege et al., 2017).
No additional carriers were found among 5198 AD cases and 4491 controls from the Alzheimer’s Disease Sequencing Project from whom whole-exome sequencing data were available, 1779 AD cases and 1273 controls from the Alzheimer Disease Exome Sequencing France project, 332 cases and 676 controls of European ancestry from the United Kingdom and North America (Campion et al., 2019), or 1255 cases and 1938 controls in a pan-European cohort from the European Early Onset Dementia Consortium (Holstege et al., 2017).
The D1620V variant is classified as “uncertain: possibly pathogenic” by the criteria of Holstege et al. (Holstege et al., 2017).
Functional Consequences
The D1620V 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
References
Paper Citations
- Holstege H, van der Lee SJ, Hulsman M, Wong TH, van Rooij JG, Weiss M, Louwersheimer E, Wolters FJ, Amin N, Uitterlinden AG, Hofman A, Ikram MA, van Swieten JC, Meijers-Heijboer H, van der Flier WM, Reinders MJ, van Duijn CM, Scheltens P. Characterization of pathogenic SORL1 genetic variants for association with Alzheimer's disease: a clinical interpretation strategy. Eur J Hum Genet. 2017 Aug;25(8):973-981. Epub 2017 May 24 PubMed.
- Campion D, Charbonnier C, Nicolas G. 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
- Holstege H, van der Lee SJ, Hulsman M, Wong TH, van Rooij JG, Weiss M, Louwersheimer E, Wolters FJ, Amin N, Uitterlinden AG, Hofman A, Ikram MA, van Swieten JC, Meijers-Heijboer H, van der Flier WM, Reinders MJ, van Duijn CM, Scheltens P. Characterization of pathogenic SORL1 genetic variants for association with Alzheimer's disease: a clinical interpretation strategy. Eur J Hum Genet. 2017 Aug;25(8):973-981. Epub 2017 May 24 PubMed.
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