ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.806G>A (p.Arg269His) (rs63750900)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000689465 SCV000817117 pathogenic Alzheimer disease, type 3; Frontotemporal dementia; Pick's disease; Acne inversa, familial, 3 2018-11-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 269 of the PSEN1 protein (p.Arg269His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs63750900, ExAC 0.01%). This variant has been observed in individuals and families affected with Alzheimer's disease (PMID: 9189043, 27777022, 28350801, 9804121, Invitae). ClinVar contains an entry for this variant (Variation ID: 38297). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. The p.Arg269 amino acid residue in PSEN1 has been determined to be clinically significant (PMID: 8910898, 15205973, 27930341). This suggests that variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000031858 SCV000054464 pathologic Alzheimer disease, type 4 2010-12-23 no assertion criteria provided curation Converted during submission to Pathogenic.
VIB Department of Molecular Genetics, University of Antwerp RCV000084374 SCV000116510 not provided not provided no assertion provided not provided

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