ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.1292C>T (p.Ala431Val)

dbSNP: rs63750083
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000084412 SCV000843411 uncertain significance not provided 2017-12-29 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV002288582 SCV002579440 likely pathogenic Frontotemporal dementia 2021-08-11 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005222750 SCV005863535 pathogenic Alzheimer disease 3; Frontotemporal dementia; Pick disease; Acne inversa, familial, 3 2024-12-30 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 431 of the PSEN1 protein (p.Ala431Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Alzheimer's disease (PMID: 12399144, 27799753; internal data). ClinVar contains an entry for this variant (Variation ID: 98113). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt PSEN1 protein function with a positive predictive value of 95%. This variant disrupts the p.Ala431 amino acid residue in PSEN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16628450, 16897084). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
VIB Department of Molecular Genetics, University of Antwerp RCV000084412 SCV000116548 not provided not provided no assertion provided not provided

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