Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001212263 | SCV001383843 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2022-07-19 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1684 of the SCN1A protein (p.Tyr1684Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of SCN1A-related conditions (PMID: 14738421; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 942302). 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. This variant disrupts the p.Tyr1684 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been observed in individuals with SCN1A-related conditions (PMID: 21248271), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
| Institute for Human Genetics and Genomic Medicine, |
RCV004699130 | SCV005201051 | pathogenic | Severe myoclonic epilepsy in infancy | criteria provided, single submitter | clinical testing | The detected variant is not present in gnomAD. In literature, the variant has been reported in individuals with SCN1A associated epilepsy (PMID: 14738421, PMID 34226156). Bioinformatic prediction tools anticipate a deleterious effect, the variant was ranked pathogenic (ACMG: PS1, PS2, PM2, PP3). |