Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001218504 | SCV001390388 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2020-08-26 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with SCN1A-related conditions. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in SCN1A are known to be pathogenic (PMID: 17347258, 18930999). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser628*) in the SCN1A gene. It is expected to result in an absent or disrupted protein product. |
| Victorian Clinical Genetics Services, |
RCV004594251 | SCV005086045 | pathogenic | Severe myoclonic epilepsy in infancy | 2024-09-21 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Loss of function and gain of function are known mechanisms of disease in this gene and are associated with SCN1A-related epilepsy (PMID: 28488083). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0112 - The condition associated with this gene has incomplete penetrance. Reduced penetrance has been described for generalized epilepsy with febrile seizures plus, type 2 (MIM#604403) (PMID: 20301494). (I) 0115 - Variants in this gene are known to have variable expressivity. Inter-familial and intra-familial variable expressivity has been observed (PMID: 20301494). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |