ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.1292C>A (p.Ala431Glu) (rs63750083)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000517533 SCV000614819 pathogenic not provided 2015-12-30 criteria provided, single submitter clinical testing
Invitae RCV000640606 SCV000762200 pathogenic Alzheimer disease, type 3; Frontotemporal dementia; Pick's disease; Acne inversa, familial, 3 2018-09-11 criteria provided, single submitter clinical testing This sequence change replaces alanine with glutamic acid at codon 431 of the PSEN1 protein (p.Ala431Glu). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with autosomal dominant Alzheimer disease in several families of Mexican descent and this variant is considered a founder mutation originating from individuals from Jalisco state in Mexico (PMID: 16897084, 16628450). ClinVar contains an entry for this variant (Variation ID: 18155). Experimental studies have shown that this missense change impairs the function of the presenilin-1 protein including inhibiting the gamma secretase activity and its function as a calcium leak channel (PMID: 20634584, 27930341, 20145736, 21373759). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000019785 SCV000040083 pathogenic Alzheimer disease, type 3 2006-11-01 no assertion criteria provided literature only
GeneReviews RCV000019785 SCV000040381 pathologic Alzheimer disease, type 3 2010-12-23 no assertion criteria provided curation Converted during submission to Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.