Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000807776 | SCV000947848 | uncertain significance | Familial hemophagocytic lymphohistiocytosis 5 | 2022-08-09 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 459 of the STXBP2 protein (p.Arg459Gln). This variant is present in population databases (rs201164454, gnomAD 0.05%), including at least one homozygous and/or hemizygous individual. 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: 652253). 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. 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. |
Ambry Genetics | RCV002537269 | SCV003729215 | uncertain significance | Inborn genetic diseases | 2022-11-09 | criteria provided, single submitter | clinical testing | The c.1376G>A (p.R459Q) alteration is located in exon 16 (coding exon 16) of the STXBP2 gene. This alteration results from a G to A substitution at nucleotide position 1376, causing the arginine (R) at amino acid position 459 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |