ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.236C>T (p.Ala79Val) (rs63749824)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000529477 SCV000639604 pathogenic Alzheimer disease, type 3; Frontotemporal dementia; Pick's disease; Acne inversa, familial, 3 2017-07-12 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 79 of the PSEN1 protein (p.Ala79Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs63749824, ExAC 0.001%). This variant has been reported to segregate with late-onset Alzheimer's disease in a single family; however, segregation was not complete in this family (PMID: 27454811). In addition, this variant has been reported in several individuals affected with early-onset Alzheimer's disease (PMID: 9384602, 10631141). ClinVar contains an entry for this variant (Variation ID: 18157). Experimental studies have shown that this missense change does not affect PSEN1-related calcium channel function but does result in an increase in the more fibrillogenic amyloid beta 42 peptide (PMID: 17431506, 17366635). For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics Inc RCV000084281 SCV000843412 pathogenic not provided 2015-10-13 criteria provided, single submitter clinical testing
OMIM RCV000019787 SCV000040085 pathogenic Alzheimer disease, type 3 2007-05-01 no assertion criteria provided literature only
GeneReviews RCV000019787 SCV000040382 pathologic Alzheimer disease, type 3 2010-12-23 no assertion criteria provided curation Converted during submission to Pathogenic.
VIB Department of Molecular Genetics, University of Antwerp RCV000084281 SCV000116417 not provided not provided no assertion provided not provided

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