ClinVar Miner

Submissions for variant NM_014191.4(SCN8A):c.802A>C (p.Ile268Leu) (rs1085308013)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489449 SCV000577829 likely pathogenic not provided 2015-04-18 criteria provided, single submitter clinical testing The I268L variant in the SCN8A gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The I268L variant was not observed in approximately 6400 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 I268L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is well-conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in a nearby residue (F260S) has been reported in the Human Gene Mutation Database in association with epileptic encephalopathy (Stenson et al., 2014), supporting the functional importance of this region of the protein. The I268L variant is a strong candidate for a disease-causing variant however, the possibility it may be a rare benign variant cannot be excluded.

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