Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000483871 | SCV000571528 | likely pathogenic | not provided | 2016-08-30 | criteria provided, single submitter | clinical testing | The E1836X variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The E1836X likely pathogenic variant is predicted to cause loss of normal protein function through protein truncation, as the last 174 amino acids of the SCN1A protein are lost. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
Invitae | RCV001232515 | SCV001405077 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu1836*) in the SCN1A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 174 amino acid(s) of the SCN1A protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 422136). This variant disrupts a region of the SCN1A protein in which other variant(s) (p.Arg1912*) have been determined to be pathogenic (PMID: 14738421, 23195492; 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. |