ClinVar Miner

Submissions for variant NM_001377265.1(MAPT):c.2078C>T (p.Pro693Leu) (rs63751273)

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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 RCV000084527 SCV000614049 pathogenic not provided 2016-08-30 criteria provided, single submitter clinical testing
Invitae RCV000015313 SCV000813769 pathogenic Frontotemporal dementia 2020-08-04 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 301 of the MAPT protein (p.Pro301Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with frontotemporal dementia in several families (PMID: 9641683, 26220942, 27439681). ClinVar contains an entry for this variant (Variation ID: 14245). Experimental studies have shown that this missense change alters microtubule binding with altered MAPT isoform ratio leading to the formation of neurofibrillary tangles (PMID: 9641683, 26269332, 25592136, 26220942, 11756436). Mouse models recapitulate the human frontotemporal dementia phenotype (PMID: 22723997, 26519432, 22022446). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000763405 SCV000894132 pathogenic Frontotemporal dementia; Parkinson disease, late-onset; Parkinson-dementia syndrome; Pick disease; Progressive supranuclear ophthalmoplegia 2018-10-31 criteria provided, single submitter clinical testing
Institute of Human Genetics, Klinikum rechts der Isar RCV000015313 SCV001150159 pathogenic Frontotemporal dementia 2018-01-22 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000084527 SCV001961704 pathogenic not provided 2021-09-01 criteria provided, single submitter clinical testing
OMIM RCV000015313 SCV000035572 pathogenic Frontotemporal dementia 2009-07-14 no assertion criteria provided literature only
OMIM RCV000015314 SCV000035573 pathogenic Progressive supranuclear ophthalmoplegia 2009-07-14 no assertion criteria provided literature only
VIB Department of Molecular Genetics, University of Antwerp RCV000084527 SCV000116663 not provided not provided no assertion provided not provided

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