ClinVar Miner

Submissions for variant NM_000484.4(APP):c.2143G>A (p.Val715Met)

dbSNP: rs63750734
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000084570 SCV000612389 likely pathogenic not provided 2017-06-23 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000019724 SCV003925659 pathogenic Alzheimer disease type 1 2023-05-05 criteria provided, single submitter clinical testing Criteria applied: PS3,PS4_MOD,PM1,PM5,PM2_SUP,PP3
Suna and Inan Kirac Foundation Neurodegeneration Research Laboratory, Koc University RCV000019724 SCV003932785 pathogenic Alzheimer disease type 1 2023-03-21 criteria provided, single submitter research This case has this variant as heterozygous
Invitae RCV003509483 SCV004297369 pathogenic Alzheimer disease 2023-08-02 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 715 of the APP protein (p.Val715Met). This missense change has been observed in individuals with early-onset Alzheimer disease (PMID: 10441572, 18437002; Invitae). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects APP function (PMID: 10097173, 11487570, 20452985). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt APP protein function. ClinVar contains an entry for this variant (Variation ID: 18097).
OMIM RCV000019724 SCV000040022 pathogenic Alzheimer disease type 1 1999-09-01 no assertion criteria provided literature only
VIB Department of Molecular Genetics, University of Antwerp RCV000084570 SCV000116706 not provided not provided no assertion provided not provided

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