Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Bioinformatics, |
RCV000180822 | SCV000221786 | pathogenic | Severe myoclonic epilepsy in infancy | 2014-12-20 | criteria provided, single submitter | research | |
Athena Diagnostics Inc | RCV000180822 | SCV000255819 | pathogenic | Severe myoclonic epilepsy in infancy | 2015-04-15 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000412755 | SCV000490893 | pathogenic | not provided | 2017-07-06 | criteria provided, single submitter | clinical testing | The R931H pathogenic variant in the SCN1A gene has been reported multiple times in association with SCN1A-related disorders (Zuberi et al., 2011; Catarino et al., 2011; Rilstone et al., 2012). 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 R931H variant is a conservative amino acid substitution. This substitution occurs at a conserved position predicted to be within the pore forming loop between the S5 and S6 transmembrane segments of the second homologous domain. Different missense variants in the same residue (R931C, R931P) as well as multiple missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with SCN1A-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, the presence of the R931H variant is consistent with the diagnosis of a SCN1A-related disorder. |
Invitae | RCV000457088 | SCV000548777 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2022-09-07 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with Dravet syndrome (PMID: 22780858, 25243660, 27231140, 28079314). In at least one individual the variant was observed to be de novo. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg931 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12083760, 18076640). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SCN1A protein function. ClinVar contains an entry for this variant (Variation ID: 189869). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 931 of the SCN1A protein (p.Arg931His). |
Fulgent Genetics, |
RCV000763459 | SCV000894236 | pathogenic | Migraine, familial hemiplegic, 3; Severe myoclonic epilepsy in infancy; Generalized epilepsy with febrile seizures plus, type 2 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Center of Excellence for Medical Genomics, |
RCV002281565 | SCV002570035 | pathogenic | Migraine, familial hemiplegic, 3 | 2002-09-08 | no assertion criteria provided | research |