ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.347C>T (p.Thr116Ile)

dbSNP: rs63750730
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002514493 SCV003442898 pathogenic Alzheimer disease 3; Frontotemporal dementia; Pick disease; Acne inversa, familial, 3 2022-04-11 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 116 of the PSEN1 protein (p.Thr116Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with early-onset Alzheimer disease (PMID: 15272895, 16033913, 28008242, 30200536). ClinVar contains an entry for this variant (Variation ID: 98016). 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. This variant disrupts the p.Thr116 amino acid residue in PSEN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10439444, 18667258, 27930341, 29404783). 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 RCV000084296 SCV000116432 not provided not provided no assertion provided not provided

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