ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.428T>C (p.Ile143Thr)

dbSNP: rs63750004
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000084308 SCV000614821 pathogenic not provided 2016-02-01 criteria provided, single submitter clinical testing
Invitae RCV001071503 SCV001236811 pathogenic Alzheimer disease 3; Frontotemporal dementia; Pick disease; Acne inversa, familial, 3 2023-09-13 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 98026). This missense change has been observed in individuals with early-onset Alzheimer's disease (PMID: 8634711, 17968601, 20628413, 24773620, 28350801, 30090657, 30528841). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 143 of the PSEN1 protein (p.Ile143Thr). 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 PSEN1 protein function. Experimental studies have shown that this missense change affects PSEN1 function (PMID: 19276550, 19276551, 22508690, 27930341). For these reasons, this variant has been classified as Pathogenic.
VIB Department of Molecular Genetics, University of Antwerp RCV000084308 SCV000116444 not provided not provided no assertion provided not provided

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