ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.626G>T (p.Gly209Val) (rs63750053)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000640604 SCV000762198 pathogenic Alzheimer disease, type 3; Frontotemporal dementia; Pick's disease; Acne inversa, familial, 3 2017-10-27 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 209 of the PSEN1 protein (p.Gly209Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with familial Alzheimer disease in a family (PMID: 9521423).  This variant has also been reported in several individuals affected with familial Alzheimer disease (PMID: 9521418, 24773620, 10468510,). ClinVar contains an entry for this variant (Variation ID: 98053). Experimental studies have shown that this missense change impairs protein function (PMID: 27930341, 10468510, 17197420, 26923592). Several missense substitutions at this codon (p.Gly209Ala, p.Gly209Arg, p.Gly209Glu) have been observed in individuals affected with familial Alzheimer disease (PMID: 27206484, 10447269, 11524469). This suggests that the glycine residue is critical for PSEN1 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
VIB Department of Molecular Genetics, University of Antwerp RCV000084340 SCV000116476 not provided not provided no assertion provided not provided

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