ClinVar Miner

Submissions for variant NM_000484.4(APP):c.2080G>A (p.Asp694Asn) (rs63749810)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000687111 SCV000814663 pathogenic Alzheimer disease 2018-02-17 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 694 of the APP protein (p.Asp694Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant, also known as the amyloid-_x0001_beta _x0001_D23N Iowa mutation, has been reported in numerous individuals and families affected with cerebral amyloid angiopathy (CAA) (PMID: 27000221, 20228223, 26104569, 27858710, 24878480, 28350801). This variant has also been reported to segregate with CAA in several families (PMID: 26104569, 27858710, 24878480, 28350801). ClinVar contains an entry for this variant (Variation ID: 18101). Experimental studies have shown that this missense change results in protein aggregation propensity, proteolytic breakdown of smooth muscle cell-actin, and increased cell death (PMID: 26402770, 11441013). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000019729 SCV000040027 pathogenic ABeta amyloidosis, Iowa type 2003-03-25 no assertion criteria provided literature only
VIB Department of Molecular Genetics, University of Antwerp RCV000084564 SCV000116700 not provided not provided no assertion provided not provided

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