ClinVar Miner

Submissions for variant NM_001377265.1(MAPT):c.2091+16C>T (rs63751011)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000084537 SCV000614050 pathogenic not provided 2017-04-04 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626752 SCV000747455 pathogenic Dementia 2017-01-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626753 SCV000747456 pathogenic Frontotemporal dementia; Memory impairment; Mental deterioration 2017-01-01 criteria provided, single submitter clinical testing
Invitae RCV000687510 SCV000815082 pathogenic Frontotemporal dementia 2020-02-01 criteria provided, single submitter clinical testing This sequence change falls in intron 9 of the MAPT gene. It does not directly change the encoded amino acid sequence of the MAPT protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with frontotemporal dementia in many families (PMID: 9641683, 28097206, 19786698, 11912108, 20045477, 11708988, 17923640, 11971081, 19766248) and likely represents a founder mutation originating from Northern Wales (PMID:19365643). This variant is also known as IVS10+16C>T or 10+16C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 98222). Experimental studies have shown that this intronic change disrupts the stem-loop structure thus leading to aberrant splicing and increased incorporation of exon 10 of MAPT mRNA (PMID: 9641683, 10329720, 26136155, 19914360). Mouse models recapitulate the human frontotemporal dementia phenotype (PMID:23680655). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, Klinikum rechts der Isar RCV000687510 SCV001150160 pathogenic Frontotemporal dementia 2018-01-23 criteria provided, single submitter clinical testing
GeneDx RCV000084537 SCV001767383 pathogenic not provided 2021-08-30 criteria provided, single submitter clinical testing Published functional studies demonstrate that this variant leads to aberrant splicing of exon 10 (Umeda et al., 2013; Hutton et al., 1998); Not observed at significant frequency in large population cohorts (Lek et al., 2016); Nearby splice variants reported in the Human Gene Mutation Database (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 19365643, 27905268, 23885714, 10443890, 7783864, 8940276, 23680655, 19914360, 26136155, 27082848, 28097206, 29253099, 29930232, 11402146, 27594586, 25683866, 20045477, 19786698, 18525295, 14755449, 11708988, 11641718, 10446810, 10202939, 9392579, 9088499, 7936288, 11255441, 31031559, 31537715, 9641683, 19884572, 12847166, 15372253, 17923640, 19766248, 11971081, 11971082, 11912108)
OMIM RCV000687510 SCV000035578 pathogenic Frontotemporal dementia 2009-10-01 no assertion criteria provided literature only
VIB Department of Molecular Genetics, University of Antwerp RCV000084537 SCV000116673 not provided not provided no assertion provided not provided

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