ClinVar Miner

Submissions for variant NM_016835.4(MAPT):c.1789_1791AAG[1] (p.Lys598del) (rs63750688)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000695531 SCV000824037 uncertain significance Frontotemporal dementia 2018-06-12 criteria provided, single submitter clinical testing This variant, c.841_843delAAG, results in the deletion of 1 amino acid of the MAPT protein (p.Lys281del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs755349386, ExAC 0.1%). This variant has been observed in individuals affected with frontotemporal dementia and Alzheimer's disease (PMID: 9973279, 17723255). This variant is also known as p.Lys280del and ΔK280 in the literature. ClinVar contains an entry for this variant (Variation ID: 98213). Experimental studies have shown that this amino acid deletion significantly reduces the protein's ability to promote microtubule assembly compared to wild type protein (PMID: 9973279). Additionally, this variant alters protein conformation resulting in increased propensity to form tau aggregates (PMID: 18725924, 24448233, 23515417). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Institute of Human Genetics,Klinikum rechts der Isar RCV000695531 SCV001150158 likely pathogenic Frontotemporal dementia 2019-06-07 criteria provided, single submitter clinical testing
VIB Department of Molecular Genetics, University of Antwerp RCV000084522 SCV000116658 not provided not provided no assertion provided not provided

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.