Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001947096 | SCV002242807 | pathogenic | Alzheimer disease | 2023-12-08 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 716 of the APP protein (p.Ile716Val). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This missense change has been observed in individuals with clinical features of Alzheimer disease (PMID: 9328472; Invitae). ClinVar contains an entry for this variant (Variation ID: 1457308). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this missense change affects APP function (PMID: 9328472, 11487570, 20452985, 24117942). This variant disrupts the p.Ile716 amino acid residue in APP. Other variant(s) that disrupt this residue have been observed in individuals with APP-related conditions (PMID: 18667258, 24117942), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
Ce |
RCV005242139 | SCV005893585 | pathogenic | not provided | 2024-12-01 | criteria provided, single submitter | clinical testing | APP: PM1, PM2, PM5, PS3:Moderate, PS4:Moderate |