Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001068032 | SCV001233120 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2022-04-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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: 861493). This variant is also known as p.Leu990Phe. This missense change has been observed in individual(s) with Dravet syndrome (PMID: 31864146). 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 replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 991 of the SCN1A protein (p.Leu991Phe). |
| 3billion | RCV001809976 | SCV002059065 | likely pathogenic | Severe myoclonic epilepsy in infancy | 2022-01-03 | criteria provided, single submitter | clinical testing | The variant has been previously reported as de novo in a similarly affected individual (PS2_S). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with SCN1A related disorder (PMID:31864146, PS1_P). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.882, 3CNET: 0.987, PP3_P). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |