Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001889533 | SCV002164909 | uncertain significance | Familial hemophagocytic lymphohistiocytosis 5 | 2022-08-15 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 587 of the STXBP2 protein (p.Leu587Val). This variant is present in population databases (rs756684008, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with STXBP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1390378). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
| Genome Diagnostics Laboratory, |
RCV002264417 | SCV002542996 | uncertain significance | Autoinflammatory syndrome | 2018-08-01 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002553568 | SCV003653772 | uncertain significance | Inborn genetic diseases | 2021-08-04 | criteria provided, single submitter | clinical testing | The c.1759C>G (p.L587V) alteration is located in exon 19 (coding exon 19) of the STXBP2 gene. This alteration results from a C to G substitution at nucleotide position 1759, causing the leucine (L) at amino acid position 587 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |