Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuro |
RCV000059418 | SCV000693759 | likely pathogenic | Severe myoclonic epilepsy in infancy | 2018-01-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000812820 | SCV000953146 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2018-11-07 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro1451 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 21248271, 26096185), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed to be de novo in an individual affected with severe myoclonic epilepsy in infancy (SMEI) also known as Dravet syndrome (PMID: 17054684). ClinVar contains an entry for this variant (Variation ID: 68544). This sequence change replaces proline with leucine at codon 1451 of the SCN1A protein (p.Pro1451Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. |
Génétique des Maladies du Développement, |
RCV003224861 | SCV003852745 | pathogenic | See cases | 2022-10-26 | criteria provided, single submitter | clinical testing | |
Uni |
RCV000059418 | SCV000090942 | not provided | Severe myoclonic epilepsy in infancy | no assertion provided | not provided |