ClinVar Miner

Submissions for variant NM_014191.4(SCN8A):c.3943G>T (p.Val1315Leu) (rs1555228303)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498624 SCV000590727 likely pathogenic not provided 2017-06-23 criteria provided, single submitter clinical testing A novel c.3943 G>T variant that is likely pathogenic has been identified in the SCN8A gene. The c.3943 G>T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.3943 G>T variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Several in-silico splice prediction models predict that c.3943 G>T may damage the natural splice acceptor site and lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. If c.3943 G>T does not alter splicing, it will result in the V1315L missense change, which is a conservative amino acid substitution. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. A different missense substitution at the same position (V1315M) has been reported previously as a de novo change in an individual with early infantile epileptic encephalopathy (Trump et al., 2016). Therefore, the V1315L variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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