Total submissions: 4
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, |
RCV000695531 | SCV001150158 | likely pathogenic | Frontotemporal dementia | 2019-06-07 | criteria provided, single submitter | clinical testing | |
Gene |
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, |
RCV000084522 | SCV000116658 | not provided | not provided | no assertion provided | not provided |