ClinVar Miner

Submissions for variant NM_001377265.1(MAPT):c.2014AAG[1] (p.Lys673del) (rs63750688)

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Total submissions: 3
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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

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