Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001045702 | SCV001209571 | uncertain significance | Familial hemophagocytic lymphohistiocytosis 5 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 573 of the STXBP2 protein (p.Pro573Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs768637937, ExAC 0.006%). This missense change has been observed in individual(s) with hemophagocytic lymphohistiocytosis (PMID: 24194549). ClinVar contains an entry for this variant (Variation ID: 843150). 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"). 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. |
| Ce |
RCV002264153 | SCV002546056 | uncertain significance | not provided | 2022-05-01 | criteria provided, single submitter | clinical testing | STXBP2: PM2, PM3:Supporting |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004702598 | SCV005205360 | uncertain significance | not specified | 2024-06-04 | criteria provided, single submitter | clinical testing | Variant summary: STXBP2 c.1718C>T (p.Pro573Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251268 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1718C>T has been reported in the literature in an individual affected with Familial Hemophagocytic Lymphohistiocytosis (example: Shabrish_2021). This report does not provide unequivocal conclusions about association of the variant with Familial Hemophagocytic Lymphohistiocytosis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 33746956). ClinVar contains an entry for this variant (Variation ID: 843150). Based on the evidence outlined above, the variant was classified as uncertain significance. |