Overview

Pathogenicity: Frontotemporal Dementia : Benign
Clinical Phenotype: None
Reference Assembly: GRCh37/hg19
Position: Chr17:44060769 G>A
dbSNP ID: rs757159453
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: GGG to GAG
Reference Isoform: Tau Isoform Tau-G (776 aa)
Genomic Region: Exon 4a

Findings

This variant in MAPT was found in an exome sequencing study of 141 Caucasian individuals with late-onset Alzheimer’s disease and 179 elderly Caucasian controls without neuropathology. Specifically, it was detected in one control individual with an APOE genotype of ε3/ε3 (Sassi et al., 2014).

Note that exon 4a is excluded from the six major tau isoforms expressed in the human brain, but it is present in PNS-tau (P10636-1) and Tau-G (P10636-9), which are 758 and 776 amino acids long, respectively. Therefore, the position of this variant is in reference to these isoforms, rather than to isoform Tau-F (P10636-8).

Neuropathology

Not applicable.

Biological Effect

Unknown. In silico, this variant is predicted to be “possibly damaging.” It is classified as a benign polymorphism according to the algorithm proposed by Guerreiro et al., 2010 (Sassi et al., 2014).

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References

Paper Citations

1. Sassi C, Guerreiro R, Gibbs R, Ding J, Lupton MK, Troakes C, Al-Sarraj S, Niblock M, Gallo JM, Adnan J, Killick R, Brown KS, Medway C, Lord J, Turton J, Bras J, Alzheimer's Research UK Consortium, Morgan K, Powell JF, Singleton A, Hardy J. Investigating the role of rare coding variability in Mendelian dementia genes (APP, PSEN1, PSEN2, GRN, MAPT, and PRNP) in late-onset Alzheimer's disease. Neurobiol Aging. 2014 Dec;35(12):2881.e1-2881.e6. Epub 2014 Jun 16 PubMed.
2. Guerreiro RJ, Baquero M, Blesa R, Boada M, Brás JM, Bullido MJ, Calado A, Crook R, Ferreira C, Frank A, Gómez-Isla T, Hernández I, Lleó A, Machado A, Martínez-Lage P, Masdeu J, Molina-Porcel L, Molinuevo JL, Pastor P, Pérez-Tur J, Relvas R, Oliveira CR, Ribeiro MH, Rogaeva E, Sa A, Samaranch L, Sánchez-Valle R, Santana I, Tàrraga L, Valdivieso F, Singleton A, Hardy J, Clarimón J. Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP. Neurobiol Aging. 2010 May;31(5):725-31. Epub 2008 Jul 30 PubMed.

External Citations

1. P10636-1
2. P10636-9
3. P10636-8

Further Reading

No Available Further Reading