Submissions for variant NC_000009.11:g.(?_129376729)_(131016993_?)del

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001383155	SCV001582196	pathogenic	Early infantile epileptic encephalopathy with suppression bursts	2020-05-20	criteria provided, single submitter	clinical testing	A gross deletion of the genomic region encompassing the full coding sequence of the STXBP1 gene has been identified. The boundaries of this event are unknown as the deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. Isolated whole-gene deletions of STXBP1 have not been reported in the literature. However, larger copy number events that include this gene have been observed in individuals affected with epilepsy (PMID:26865513, 22722545, 29264391, 26514728, 18469812 , Invitae). Loss-of-function variants in STXBP1 are known to be pathogenic (PMID: 20887364, 26384463). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001364955	SCV001561166	uncertain significance	Developmental and epileptic encephalopathy, 31A	2020-05-20	flagged submission	clinical testing	A gross deletion of the genomic region encompassing the full coding sequence of the DNM1 gene has been identified. The boundaries of this event are unknown as the deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals with a DNM1-related disease. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in DNM1 cause disease. 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.