Mutations

SORL1 S1958C

Overview

Clinical Phenotype: Alzheimer's Disease
Position: (GRCh38/hg38):Chr11:121619901 C>G
Position: (GRCh37/hg19):Chr11:121490610 C>G
dbSNP ID: rs768270783
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected Protein Consequence: Missense
Codon Change: TCT to TGT
Reference Isoform: SORL1 Isoform 1 (2214 aa)
Genomic Region: Exon 43

Findings

In a European cohort of 1255 Alzheimer’s cases and 1938 controls, a German AD case was found to be a heterozygous carrier of this variant (Verheijen et al., 2016).

No additional carriers were found in a Dutch sample of 640 AD cases and 1268 controls (Holstege et al., 2017).

The S1958C variant is classified as possibly pathogenic by the criteria of Holstege et al. (Holstege et al., 2017).

Functional Consequences

The variant was predicted to be damaging by SIFT, disease-causing by Mutation Taster, and possibly damaging by PolyPhen-2 (Verheijen et al., 2016).

Last Updated: 18 Jul 2024

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References

Paper Citations

  1. Verheijen J, Van den Bossche T, van der Zee J, Engelborghs S, Sanchez-Valle R, Lladó A, Graff C, Thonberg H, Pastor P, Ortega-Cubero S, Pastor MA, Benussi L, Ghidoni R, Binetti G, Clarimon J, Lleó A, Fortea J, de Mendonça A, Martins M, Grau-Rivera O, Gelpi E, Bettens K, Mateiu L, Dillen L, Cras P, De Deyn PP, Van Broeckhoven C, Sleegers K. A comprehensive study of the genetic impact of rare variants in SORL1 in European early-onset Alzheimer's disease. Acta Neuropathol. 2016 Aug;132(2):213-24. Epub 2016 Mar 30 PubMed.
  2. 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.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. Verheijen J, Van den Bossche T, van der Zee J, Engelborghs S, Sanchez-Valle R, Lladó A, Graff C, Thonberg H, Pastor P, Ortega-Cubero S, Pastor MA, Benussi L, Ghidoni R, Binetti G, Clarimon J, Lleó A, Fortea J, de Mendonça A, Martins M, Grau-Rivera O, Gelpi E, Bettens K, Mateiu L, Dillen L, Cras P, De Deyn PP, Van Broeckhoven C, Sleegers K. A comprehensive study of the genetic impact of rare variants in SORL1 in European early-onset Alzheimer's disease. Acta Neuropathol. 2016 Aug;132(2):213-24. Epub 2016 Mar 30 PubMed.

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