ClinVar Miner

Submissions for variant NM_016835.4(MAPT):c.2038G>A (p.Val680Ile) (rs63750869)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen 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, University of Antwerp RCV000084551 SCV000116687 not provided not provided no assertion provided not provided

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