ClinVar Miner

Submissions for variant NM_014191.4(SCN8A):c.4913G>A (p.Arg1638His) (rs1064794873)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485665 SCV000570126 likely pathogenic not provided 2016-05-11 criteria provided, single submitter clinical testing The R1638H variant has not been published as a pathogenic variant in association with human disease, nor has it been reported as a benign variant to our knowledge. Functional studies suggest that the R1638H variant alters the inactivation time constant as well as the gating current immobilization of the sodium channel (Kuhn et al., 1999). It was not observed in approximately 6,500 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 occurs at a conserved position predicted to be within the voltage-sensor transmembrane segment S4 in the fourth homologous domain of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the R1638H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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