Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001229412 | SCV001401857 | likely pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2024-10-16 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 201 of the SCN1A protein (p.Ala201Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of SCN1A-related conditions (PMID: 30368457, 35074891; internal data). ClinVar contains an entry for this variant (Variation ID: 956579). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Arg201 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28079314). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |