Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Genomics, |
RCV002208785 | SCV002495977 | uncertain significance | Familial hemophagocytic lymphohistiocytosis 5 | 2021-07-26 | criteria provided, single submitter | clinical testing | STXBP2 NM_006949.3 exon 14 p.Leu409Phe (c.1225C>T): This variant has not been reported in the literature but is present in 0.02% (1/4834) of South Asian alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/19-7644731-C-T?dataset=gnomad_r3). Evolutionary conservation suggests that this variant may impact the protein; computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
Labcorp Genetics |
RCV002208785 | SCV002983232 | uncertain significance | Familial hemophagocytic lymphohistiocytosis 5 | 2022-06-05 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 409 of the STXBP2 protein (p.Leu409Phe). This variant is present in population databases (rs763024326, gnomAD 0.006%). 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: 1675137). 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: "Tolerated"; 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. |