Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002514122 | SCV003442734 | pathogenic | Alzheimer disease 3; Frontotemporal dementia; Pick disease; Acne inversa, familial, 3 | 2022-04-12 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 21026). 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: 24918054). This variant disrupts the p.Leu392 amino acid residue in PSEN1. Other variant(s) that disrupt this residue have been observed in individuals with PSEN1-related conditions (PMID: 16033913), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. This missense change has been observed in individuals with early-onset Alzheimer disease (PMID: 11094128; Invitae). It has also been observed to segregate with disease in related individuals. This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 392 of the PSEN1 protein (p.Leu392Pro). This variant is not present in population databases (gnomAD no frequency). |
| Gene |
RCV000020082 | SCV000040380 | not provided | Alzheimer disease 3 | no assertion provided | literature only | ||
| VIB Department of Molecular Genetics, |
RCV000084403 | SCV000116539 | not provided | not provided | no assertion provided | not provided |