Submissions for variant NM_001032221.6(STXBP1):c.1702+1G>A

dbSNP: rs796053377

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000189627	SCV000243272	pathogenic	not provided	2019-12-04	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); Deletions involving coding exons in this gene are frequently reported as pathogenic, regardless of frame prediction (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 29655203, 31344879, 30654231)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000796895	SCV000936429	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2024-02-24	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 18 of the STXBP1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of early infantile epileptic encephalopathy (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 207444). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the p.Thr574 amino acid residue in STXBP1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21770924). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center	RCV001253119	SCV001428655	pathogenic	Developmental and epileptic encephalopathy, 4	2019-03-12	criteria provided, single submitter	clinical testing	This variant was identified as de novo (maternity and paternity confirmed).
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000189627	SCV001446674	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals	RCV000578282	SCV000680114	pathogenic	STXBP1-associated neurodevelopmental disorder	2017-07-11	no assertion criteria provided	clinical testing
GenomeConnect - Simons Searchlight	RCV001265152	SCV001443187	likely pathogenic	Infantile epilepsy syndrome	2018-12-03	no assertion criteria provided	provider interpretation	Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-12-03 and interpreted as Likely Pathogenic. Variant was initially reported on 2018-10-11 by GTR ID of laboratory name 500031. The reporting laboratory might also submit to ClinVar.