ClinVar Miner

Submissions for variant NM_000484.4(APP):c.2149G>T (p.Val717Phe) (rs63750264)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000815476 SCV000955932 pathogenic Alzheimer's disease 2018-11-09 criteria provided, single submitter clinical testing This sequence change replaces valine with phenylalanine at codon 717 of the APP protein (p.Val717Phe). The valine residue is highly conserved and there is a small physicochemical difference between valine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals and families affected with early-onset Alzheimer's disease and to segregate with the disease in affected families (PMID: 1925564, 15776278). This variant is also referred to as Val642Phe in the literature. ClinVar contains an entry for this variant (Variation ID: 18089). Experimental studies have shown that this missense change results in aberrant APP processing (PMID: 7806491, 8191290, 11528419, 12707272, 20452985). Mouse models of this variant showed Alzheimer-type neuropathology (PMID: 7845465). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000019715 SCV000040013 pathogenic Alzheimer disease, type 1 1999-12-21 no assertion criteria provided literature only

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