ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.488A>G (p.His163Arg) (rs63750590)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000534810 SCV000639607 pathogenic Alzheimer disease, type 3; Frontotemporal dementia; Pick's disease; Acne inversa, familial, 3 2017-04-17 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 163 of the PSEN1 protein (p.His163Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in multiple individuals affected with early-onset Alzheimer's disease (EOAD) (PMID: 12433263, 22503161) and has been observed to segregate with autosomal dominant EOAD in several families (PMID: 7596406 , 26337232, 8733303, 27264813). ClinVar contains an entry for this variant (Variation ID: 18124). Experimental studies have shown that this missense change alters cellular calcium homeostasis (PMID: 19111578),  increases beta-amyloid peptide secretion (PMID: 8986743), and causes conformational changes at the active site of gamma-secretase (PMID: 22461631). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000019752 SCV000040050 pathogenic Alzheimer disease, type 3 1995-06-29 no assertion criteria provided literature only
VIB Department of Molecular Genetics, University of Antwerp RCV000084318 SCV000116454 not provided not provided no assertion provided not provided

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