Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001377782 | SCV001575205 | likely pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2020-06-08 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Pro480 amino acid residue in STXBP1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21770924, 24315539, 25008876, 26514728). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). This variant has been observed in individual(s) with early-onset epileptic encephalopathy (PMID: 26865513). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with serine at codon 480 of the STXBP1 protein (p.Pro480Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. |
Genome |
RCV001265519 | SCV001443663 | likely pathogenic | Infantile epilepsy syndrome | 2018-06-08 | no assertion criteria provided | provider interpretation | Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-06-08 and interpreted as Likely Pathogenic. Variant was initially reported by the Epilepsy Research Center at The University of Melbourne as likely to play a significant role and was later confirmed by GeneDx. The reporting laboratory might also submit to ClinVar. |