Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Center for Bioinformatics, |
RCV000180894 | SCV000221869 | pathogenic | Severe myoclonic epilepsy in infancy | 2014-12-20 | criteria provided, single submitter | research | |
| Invitae | RCV000699982 | SCV000828716 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2022-08-23 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 189941). This premature translational stop signal has been observed in individual(s) with severe myoclonic epilepsy of infancy (PMID: 18554359). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg612*) in the SCN1A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SCN1A are known to be pathogenic (PMID: 17347258, 18930999). |
| Centre for Inherited Metabolic Diseases, |
RCV000180894 | SCV001572552 | pathogenic | Severe myoclonic epilepsy in infancy | 2021-04-25 | criteria provided, single submitter | clinical testing | |
| Lifecell International Pvt. |
RCV000180894 | SCV003804185 | pathogenic | Severe myoclonic epilepsy in infancy | criteria provided, single submitter | clinical testing | The stop gained NM_001165963.4(SCN1A):c.1834C>T (p.Arg612Ter) has been reported to ClinVar as Pathogenic with a status of (2 stars) criteria provided, multiple submitters, no conflicts (Variation ID 189941 as of 2021-07-01). The p.Arg612Ter variant is novel (not in any individuals) in gnomAD. The p.Arg612Ter variant is novel (not in any individuals) in 1kG. This variant is predicted to cause loss of normal protein function through protein truncation. This variant is a stop gained variant which occurs in an exon of SCN1A upstream of where nonsense mediated decay is predicted to occur. This variant has been previously classified as pathogenic, indicating that the region is critical to protein function. There are 369 downstream pathogenic loss of function variants, with the furthest variant being 1314 residues downstream of this variant. This indicates that the region is critical to protein function. The gene SCN1A has a low rate of benign loss of function variants as indicated by a low upper bound of the observed/expected confidence interval 0.07. The p.Arg612Ter variant is a loss of function variant in the gene SCN1A, which is intolerant of Loss of Function variants, as indicated by the presence of existing pathogenic loss of function variant NP_001159435.1:p.M1I and 503 others. This variant has been reported to be de novo in individuals affected with severe myoclonic epilepsy of infancy by Sun H et al., 2008. Loss-of-function variants in SCN1A are known to be pathogenic by Harkin L A et al., 2007. For these reasons, this variant has been classified as Pathogenic. |