ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.2567G>A (p.Arg856Gln) (rs797045942)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000193985 SCV000248809 likely pathogenic Seizures 2014-04-21 criteria provided, single submitter clinical testing
GeneDx RCV000413708 SCV000490917 pathogenic not provided 2017-07-06 criteria provided, single submitter clinical testing The R856Q variant in the SCN2A gene has been reported previously as de novo (presumed) in an individual with Ohtahara syndrome (Moller et al., 2016). In addition, a missense variant at the same residue (R856L) has been reported previously as de novo and mosaic in an individual with epilepsy of infancy with migrating focal seizures, developmental delay, dystonia, abnormal tone, and microcephaly (Howell et al., 2015). The R856Q variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R856Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position within the transmembrane segment S4 voltage sensor of the second homologous domain that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R856Q as a pathogenic variant consistent with the intractable seizures reported in this individual.

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