ClinVar Miner

Submissions for variant NM_014191.4(SCN8A):c.2534C>T (p.Ser845Phe) (rs796053210)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189266 SCV000242898 likely pathogenic not provided 2014-12-22 criteria provided, single submitter clinical testing p.Ser845Phe (S845F) TCT>TTT: c.2534 C>T in exon 15 of the SCN8A gene (NM_014191.3). The S845F 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. The S845F variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution alters a highly conserved position in transmembrane segment S4 in the 2nd homologous domain, and in silico analysis predicts this variant is probably damaging to the protein structure/function. A missense mutation in a nearby residue (F846S) has been reported in association with migrating partial seizures of infancy. Additionally, GeneDx has identified a de novo missense mutation in a nearby residue (R850Q) in an individual with seizures. Therefore, the S845F variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in EPILEPSY panel(s).

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