Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001884165 | SCV002154665 | uncertain significance | Familial hemophagocytic lymphohistiocytosis 5 | 2022-06-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 235 of the STXBP2 protein (p.Arg235Gly). This variant is present in population databases (no rsID available, gnomAD 0.008%). This missense change has been observed in individual(s) with clinical features of hemophagocytic lymphohistiocytosis (PMID: 32542393). ClinVar contains an entry for this variant (Variation ID: 1387655). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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: 26684649, 27781387, 34249802; Invitae), which suggests that this may be a clinically significant amino acid residue. 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. |
Baylor Genetics | RCV001884165 | SCV004205644 | likely pathogenic | Familial hemophagocytic lymphohistiocytosis 5 | 2023-05-26 | criteria provided, single submitter | clinical testing |