Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003764779 | SCV004570863 | pathogenic | Alzheimer disease 3; Frontotemporal dementia; Pick disease; Acne inversa, familial, 3 | 2022-11-25 | criteria provided, single submitter | clinical testing | This missense change has been observed in individuals with early-onset Alzheimer disease (PMID: 9007097, 10468510, 24773620, 27777022). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects PSEN1 function (PMID: 11489281, 27930341). 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. ClinVar contains an entry for this variant (Variation ID: 98075). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 260 of the PSEN1 protein (p.Ala260Val). |
VIB Department of Molecular Genetics, |
RCV000084365 | SCV000116501 | not provided | not provided | no assertion provided | not provided |