Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV000084551 | SCV000493218 | likely pathogenic | not provided | 2016-08-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000692998 | SCV000820851 | uncertain significance | Frontotemporal dementia | 2018-03-09 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with isoleucine at codon 363 of the MAPT protein (p.Val363Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs63750869, ExAC 0.01%). This variant has been reported in an individual affected with early-onset posterior cortical aphasia (PCA) and a family history of cognitive decline (PMID: 24018212). It has also been reported in individuals affected with sporadic progressive nonfluent aphasia (PNFA) (PMID: 23047372, 24018212, 177121602), PCA (PMID: 23047372), semantic dementia (PMID: 20598713) and frontotemporal dementia (FTD) (PMID: 21343707), as well as in unaffected family members (PMID: 21343707). ClinVar contains an entry for this variant (Variation ID: 98231). Experimental studies have shown that this missense change leads to increased microtubule oligomerization and decreased fibrillogenesis (PMID: 24018212). 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. |
VIB Department of Molecular Genetics, |
RCV000084551 | SCV000116687 | not provided | not provided | no assertion provided | not provided |