Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001298110 | SCV001487154 | likely pathogenic | Familial hemophagocytic lymphohistiocytosis 5 | 2023-04-24 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg235 amino acid residue in STXBP2. Other variant(s) that disrupt this residue have been observed in individuals with STXBP2-related conditions (PMID: 27781387, 34330684), which suggests that this may be a clinically significant amino acid residue. 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 STXBP2 protein function. ClinVar contains an entry for this variant (Variation ID: 1001770). This missense change has been observed in individual(s) with clinical features of hemophagocytic lymphohistiocytosis (PMID: 34249802). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs757488006, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 235 of the STXBP2 protein (p.Arg235Gln). |
| Genome Diagnostics Laboratory, |
RCV002264259 | SCV002543006 | uncertain significance | Autoinflammatory syndrome | 2022-04-26 | criteria provided, single submitter | clinical testing |