ClinVar Miner

Submissions for variant NM_006949.4(STXBP2):c.474_483delinsGA (p.Cys158fs)

dbSNP: rs1599397070
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000820443 SCV000961156 pathogenic Familial hemophagocytic lymphohistiocytosis 5 2025-01-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys158Trpfs*78) in the STXBP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in STXBP2 are known to be pathogenic (PMID: 19804848, 22451424). This variant is present in population databases (rs747939788, gnomAD 0.1%). This premature translational stop signal has been observed in individuals with clinical features of STXBP2-related conditions (PMID: 22336081, 23382066, 27379089, 29599780). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001550989 SCV001771404 likely pathogenic not provided 2019-06-07 criteria provided, single submitter clinical testing Observed with a pathogenic variant on the opposite allele (in trans) in patients with FHL in the published literature (Saltzman et al., 2012; Stepensky et al., 2013), however, the same genotype described by Saltzman et al. was identified in an unrelated patient with very low B cells who did not have clinical features of FHL (Maffucci et al., 2016); please note this variant was referred to as c.474_483del_insGA or c.474_483delinsGA using alternate nomenclature in these studies; Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 29599780, 23382066, 27379089, 22336081)
Fulgent Genetics, Fulgent Genetics RCV000820443 SCV002807605 pathogenic Familial hemophagocytic lymphohistiocytosis 5 2024-02-27 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000820443 SCV003818131 uncertain significance Familial hemophagocytic lymphohistiocytosis 5 2022-01-28 criteria provided, single submitter clinical testing
Baylor Genetics RCV000820443 SCV004205626 pathogenic Familial hemophagocytic lymphohistiocytosis 5 2024-02-28 criteria provided, single submitter clinical testing

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