Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000084554 | SCV000614041 | pathogenic | not provided | 2014-11-26 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002476970 | SCV000894133 | pathogenic | Frontotemporal dementia; Parkinson disease, late-onset; Progressive supranuclear palsy-parkinsonism syndrome; Pick disease; Supranuclear palsy, progressive, 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000015316 | SCV001223220 | pathogenic | Frontotemporal dementia | 2023-04-01 | criteria provided, single submitter | clinical testing | This missense change has been observed in individuals with behavioral variant frontotemporal dementia (bvFTD), Alzheimer's disease, and/or mixed dementia with parkinsonism (PMID: 9382467, 9641683, 11117542, 11889249, 23383383, 23727082, 25942996, 26028272). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs63750424, gnomAD 0.004%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 406 of the MAPT protein (p.Arg406Trp). ClinVar contains an entry for this variant (Variation ID: 14247). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects MAPT function (PMID: 10797541, 11102510, 11756436, 19304664, 21339331, 24150109). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MAPT protein function. |
Gene |
RCV000084554 | SCV001781734 | pathogenic | not provided | 2021-09-02 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate that R406W cells show a decreased level of phosphorylation and are unable to bind to microtubules resulting in accumulation in the cytoplasm (Perez et al., 2000; Delobel et al., 2002).; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 33061333, 30924900, 30562452, 31836585, 31127772, 29370822, 30279455, 23727082, 20683187, 18587238, 10514099, 14517953, 9641683, 18284428, 11889249, 12368474, 11278002, 29253099, 25942996, 26734663, 25377499, 26028272, 26581847, 20377816, 22787795, 21849646, 18992292, 11102510, 21339331, 23105105, 19304664, 11756436, 23338682, 20634584, 24150109, 10820221, 18803694, 22368988, 23383383) |
Ce |
RCV000084554 | SCV002063631 | pathogenic | not provided | 2021-12-01 | criteria provided, single submitter | clinical testing | |
Institute of Medical Genetics and Applied Genomics, |
RCV000015316 | SCV004175704 | pathogenic | Frontotemporal dementia | 2023-12-12 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000015316 | SCV000035575 | pathogenic | Frontotemporal dementia | 2003-11-01 | no assertion criteria provided | literature only | |
VIB Department of Molecular Genetics, |
RCV000084554 | SCV000116690 | not provided | not provided | no assertion provided | not provided | ||
Genome Diagnostics Laboratory, |
RCV000084554 | SCV001977751 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000084554 | SCV001980402 | pathogenic | not provided | no assertion criteria provided | clinical testing |