Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics Inc | RCV000084311 | SCV000614822 | pathogenic | not provided | 2016-11-30 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001854473 | SCV002231314 | pathogenic | Alzheimer disease 3; Frontotemporal dementia; Pick disease; Acne inversa, familial, 3 | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 146 of the PSEN1 protein (p.Met146Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with early-onset Alzheimer's disease (PMID: 9007311, 9544835, 12552037). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 98029). 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 with a positive predictive value of 80%. This variant disrupts the p.Met146 amino acid residue in PSEN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7550356, 7596406, 10441572, 15622541, 15776278, 20164095, 23792692). 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, |
RCV000084311 | SCV000116447 | not provided | not provided | no assertion provided | not provided |