ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.1279A>G (p.Ile427Val)

gnomAD frequency: 0.00001  dbSNP: rs1398951357
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Kosik Lab, Neuroscience Research Institute, University of California Santa Barbara RCV001810077 SCV001751541 benign Alzheimer disease 3 2021-06-01 criteria provided, single submitter case-control Variant does not segregate with the illness in the family where it was identified.
Labcorp Genetics (formerly Invitae), Labcorp RCV001873794 SCV002116227 uncertain significance Alzheimer disease 3; Frontotemporal dementia; Pick disease; Acne inversa, familial, 3 2023-12-18 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 427 of the PSEN1 protein (p.Ile427Val). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with sudden unexplained death (PMID: 31847883). ClinVar contains an entry for this variant (Variation ID: 1178343). 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 not expected to disrupt PSEN1 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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