ClinVar Miner

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

dbSNP: rs63750688
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000695531 SCV000824037 uncertain significance Frontotemporal dementia 2022-04-13 criteria provided, single submitter clinical testing This variant, c.841_843del, results in the deletion of 1 amino acid(s) of the MAPT protein (p.Lys281del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs755349386, gnomAD 0.01%). This variant has been observed in individual(s) with frontotemporal dementia and Alzheimer's disease (PMID: 9973279, 10514099, 17723255). This variant is also known as p.Lys280del and ΔK280. ClinVar contains an entry for this variant (Variation ID: 98213). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects MAPT function (PMID: 9973279, 18725924, 23515417, 24448233). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 Munich, Klinikum Rechts Der Isar, Tu München RCV000695531 SCV001150158 likely pathogenic Frontotemporal dementia 2019-06-07 criteria provided, single submitter clinical testing
GeneDx RCV000084522 SCV002496223 likely pathogenic not provided 2022-03-21 criteria provided, single submitter clinical testing Published functional studies have demonstrated reduced ability to promote microtubule assembly compared to wild type protein, as well as altered protein conformation resulting in increased propensity to form tau aggregates (Rizzu et al., 1999; Vogelsberg-Ragaglia et al., 2000; Meyer et al., 2014); Previously reported in individuals with frontotemporal dementia and Alzheimer disease; however segregation information was not available (Rizzu et al., 1999; Momeni et al., 2009; Mol et al, 2021); In-frame deletion of 1 amino acids in a non-repeat region; This variant is associated with the following publications: (PMID: 19498037, 11756436, 11102510, 23515417, 18725924, 9973279, 24448233, 32843152, 32741062, 17723255, 10514099, 24453187)
VIB Department of Molecular Genetics, University of Antwerp RCV000084522 SCV000116658 not provided not provided no assertion provided not provided

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