ClinVar Miner

Submissions for variant NM_000484.4(APP):c.2061A>C (p.Lys687Asn)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen RCV003397222 SCV004102647 likely pathogenic Cerebral amyloid angiopathy, APP-related; Alzheimer disease type 1 2023-11-14 criteria provided, single submitter clinical testing The variant was not detected in the general population (gnomAD). It has not yet been reported in the dbSNP151 and ClinVar databases. In the locus-specific database Alzforum, the variant is classified as likely pathogenic. In the literature, the variant has already been described in one family in three patients with early-onset Alzheimer's disease. (PMID: 37051054) In addition, another nucleotide change at this position (c.2061A>T) with the same amino acid change was reported in a patient with early-onset Alzheimer's disease. In vitro studies showed reduced cleavage of the amyloid ßA4 precursor protein by α-secretase and increased Aß40 and Aß42 levels in the presence of this variant. (PMID: 22514144) Bioinformatically, the change is classified as "probably disease-causing" (PolyPhen2, Mutation Taster, SIFT; CADDphred 24). Based on current knowledge, the variant is classified as likely pathogenic (ACMG criteria).

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