ClinVar Miner

Submissions for variant NM_016835.4(MAPT):c.1788T>G (p.Asn596Lys) (rs63750756)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000015322 SCV000832815 pathogenic Frontotemporal dementia 2019-04-08 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 279 of the MAPT protein (p.Asn279Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with frontotemporal dementia in several families (PMID: 9789048, 10412802, 10802785, 22818528, 26295349), and has also been observed in additional individuals affected with frontotemporal dementia (PMID: 10489057, 14568818, 27082848). ClinVar contains an entry for this variant (Variation ID: 14253). Experimental studies have shown that this variant affects splicing, leading to altered MAPT isoform ratio (PMID: 10412802, 16219306, 17715352, 19498037, 26143746, 26220942, 26373282). Mouse models recapitulate the human frontotemporal dementia phenotype (PMID: 16219306, 17715352, 22169201). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000763404 SCV000894131 pathogenic Frontotemporal dementia; Parkinson disease, late-onset; Parkinson-dementia syndrome; Pick's disease; Progressive supranuclear ophthalmoplegia 2018-10-31 criteria provided, single submitter clinical testing
OMIM RCV000015322 SCV000035581 pathogenic Frontotemporal dementia 2004-10-01 no assertion criteria provided literature only
VIB Department of Molecular Genetics, University of Antwerp RCV000084521 SCV000116657 not provided not provided no assertion provided not provided

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