Submissions for variant NM_052874.5(STX1B):c.338_354+15del

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003752259	SCV004450495	pathogenic	Generalized epilepsy with febrile seizures plus, type 9	2023-03-24	criteria provided, single submitter	clinical testing	This variant disrupts a region of the STX1B protein in which other variant(s) (p.Arg115Pro) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant results in the deletion of part of exon 5 of the STX1B gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in STX1B are known to be pathogenic (PMID: 25362483). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with STX1B-related conditions.