ClinVar Miner

Submissions for variant NM_014191.4(SCN8A):c.4873G>T (p.Gly1625Trp) (rs879255708)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000442495 SCV000523845 likely pathogenic not provided 2016-08-15 criteria provided, single submitter clinical testing A novel G1625W variant that is likely pathogenic has been identified in the SCN8A gene. The G1625W variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. A different missense substitution at the same amino acid residue (G1625R) has been reported in an individual with intellectual delay, generalized myoclonic seizures, scoliosis, nystagmus, and narrow palms (Fitzgerald et al., 2015). It was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these population. The G1625W variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution alters a conserved position within transmembrane segment S4 in the fourth homologous domain. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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