Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002048500 | SCV002298277 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2021-03-09 | criteria provided, single submitter | clinical testing | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals with SCN1A-related conditions. This variant is not present in population databases (ExAC no frequency). This variant, c.926_931del, results in the deletion of 2 amino acid(s) of the SCN1A protein (p.Val309_Phe310del), but otherwise preserves the integrity of the reading frame. |
| Victorian Clinical Genetics Services, |
RCV002471221 | SCV002768969 | uncertain significance | Generalized epilepsy with febrile seizures plus, type 2 | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3A. 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) 0216 - In-frame insertion/deletion in a non-repetitive region that has low conservation. (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0309 - An alternative amino acid change in the same region has been observed in gnomAD (v2) (1 heterozygote, 0 homozygotes). (I) 0600 - Variant is located in the annotated ion transporter domain (NCBI, DECIPHER). (I) 0705 - No comparable inframe deletion variants have previous evidence for pathogenicity. However, a missense variant (p.(Val309Asp)) affecting a residue within this deleted region has been reported as a VUS (ClinVar). (I) 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) 1204 - This variant has been shown to be de novo in the proband (parental status not tested but assumed). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |