ClinVar Miner

Submissions for variant NM_001032221.6(STXBP1):c.794+1G>A

dbSNP: rs1554777496
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000596140 SCV000701892 pathogenic not provided 2016-10-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001214993 SCV001386709 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2019-05-05 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in STXBP1 are known to be pathogenic (PMID: 20887364, 26384463). Disruption of this splice site has been observed to be de novo in an individual affected with early onset epileptic encephalopathy (PMID: 28133863). ClinVar contains an entry for this variant (Variation ID: 497406). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 9 of the STXBP1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002470917 SCV002768538 pathogenic Developmental and epileptic encephalopathy, 4 2020-05-21 criteria provided, single submitter clinical testing A heterozygous canonical splice site variant, NM_003165.3(STXBP1):c.794+1G>A, has been identified in intron 9 of the STXBP1 gene. This substitution may cause aberrant splicing of exon 9 in the STXBP1 gene, and affect protein function; further testing via RNA studies is required to confirm if splicing is altered. The nucleotide at this position has very high conservation (Phylop UCSC). In silico software predicts the splice site variant to cause aberrant splicing (NetGene2, NNSPLICE, Human Splicing Finder). The variant is absent in the gnomAD population database. The variant has been previously described as pathogenic in patients with early onset epileptic encephalopathy (ClinVar, Olson, H. et al. (2017)). Subsequent analysis of parental samples indicated that this variant is de novo. Based on the information available at the time of curation, this variant has been classified as PATHOGENIC. Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign

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