Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003509494 | SCV004292976 | uncertain significance | Alzheimer disease 4 | 2023-08-14 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with early-onset Alzheimer disease (PMID: 14769392, 30279455). This variant is present in population databases (rs63750880, gnomAD 0.002%). This sequence change replaces glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 228 of the PSEN2 protein (p.Gln228Leu). ClinVar contains an entry for this variant (Variation ID: 97997). 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. 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 PSEN2 protein function. |
VIB Department of Molecular Genetics, |
RCV000084264 | SCV000116400 | not provided | not provided | no assertion provided | not provided |