Total submissions: 3
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, |
RCV000084308 | SCV000116444 | not provided | not provided | no assertion provided | not provided |