ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.617G>C (p.Gly206Ala) (rs63750082)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000518563 SCV000614823 pathogenic not provided 2016-11-22 criteria provided, single submitter clinical testing
Invitae RCV000640609 SCV000762203 pathogenic Alzheimer disease, type 3; Frontotemporal dementia; Pick's disease; Acne inversa, familial, 3 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces glycine with alanine at codon 206 of the PSEN1 protein (p.Gly206Ala). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and alanine. This variant is present in population databases (rs63750082, ExAC 0.009%). This variant has been reported to segregate with Alzheimer disease in several families (PMID: 22312439, 11710891). This variant is considered a founder mutation among individuals of Hispanic ancestry originating from the Caribbean islands and has been reported in many additional individuals affected with early and late onset Alzheimer disease (PMID: 11524469, 23114514, 27073747, 25333068, 18797263). ClinVar contains an entry for this variant (Variation ID: 18143). Experimental studies have shown that this missense change impairs the ability of the presenilin-1 component of gamma secretase to properly cleave amyloid precursor protein (APP) which can lead to an increase in amyloid plaque formation (PMID: 27930341, 11710891). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000019773 SCV000040071 pathogenic Alzheimer disease, type 3 2001-11-14 no assertion criteria provided literature only

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