ClinVar Miner

Submissions for variant NM_001377265.1(MAPT):c.2263G>A (p.Val755Ile)

gnomAD frequency: 0.00006  dbSNP: 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 Center for Human Genetics Tuebingen RCV000084551 SCV000493218 likely pathogenic not provided 2016-08-01 criteria provided, single submitter clinical testing
Invitae RCV000692998 SCV000820851 pathogenic Frontotemporal dementia 2021-11-12 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 363 of the MAPT protein (p.Val363Ile). This variant is present in population databases (rs63750869, gnomAD 0.008%). This missense change has been observed in individuals with clinical features of MAPT-related conditions (PMID: 20598713, 21343707, 23047372, 31404212; Invitae). ClinVar contains an entry for this variant (Variation ID: 98231). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects MAPT function (PMID: 24018212). This variant disrupts the p.Val363 amino acid residue in MAPT. Other variant(s) that disrupt this residue have been observed in individuals with MAPT-related conditions (PMID: 24018212), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
VIB Department of Molecular Genetics, University of Antwerp RCV000084551 SCV000116687 not provided not provided no assertion provided not provided

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