ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.839A>C (p.Glu280Ala) (rs63750231)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000701892 SCV000830715 pathogenic Alzheimer disease, type 3; Frontotemporal dementia; Pick's disease; Acne inversa, familial, 3 2018-03-01 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with alanine at codon 280 of the PSEN1 protein (p.Glu280Ala). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and alanine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with early-onset Alzheimer disease in several families (PMID: 7550356, 25471389, 22766738). ClinVar contains an entry for this variant (Variation ID: 18131). Experimental studies have shown that this missense change results in a protein with diminished gamma-secretase activity (PMID: 24217025, 22461631, 27930341). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000019759 SCV000040057 pathogenic Alzheimer disease, type 3 2015-01-13 no assertion criteria provided literature only
GeneReviews RCV000019759 SCV000040391 pathologic Alzheimer disease, type 3 2010-12-23 no assertion criteria provided curation Converted during submission to Pathogenic.

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