Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000189282 | SCV000242914 | uncertain significance | not provided | 2014-07-30 | criteria provided, single submitter | clinical testing | p.Met1600Val (ATG>GTG): c.4798 A>G in exon 27 of the SCN8A gene (NM_014191.3). The M1600V variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution alters a conserved position in transmembrane segment S3 in the 4th homologous domain. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the M1600V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In addition, missense mutations in nearby residues have not been reported in association with epilepsy. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s). |
Invitae | RCV001857653 | SCV002254626 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2023-08-02 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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. ClinVar contains an entry for this variant (Variation ID: 207124). This variant has not been reported in the literature in individuals affected with SCN8A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1600 of the SCN8A protein (p.Met1600Val). |