ClinVar Miner

Submissions for variant NM_014191.4(SCN8A):c.3979A>G (p.Ile1327Val) (rs879255704)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493549 SCV000583186 likely pathogenic not provided 2015-10-29 criteria provided, single submitter clinical testing The I1327V variant in the SCN8A gene has been reported previously in the heterozygous state in an individual with neonatal epileptic encephalopathy, multiple congenital anomalies, and movement disorders (Vaher et al., 2014). The I1327 variant has also been reported in the heterozygous state in an unrelated individual with in utero onset movement disorder, epileptic encephalopahy, and developmental delay (Singh et al., 2015). The I1327V variant 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 populations. This substitution occurs at a position within the predicted S5 transmembrane segment of third homologous domain that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the I1327V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. The I1327V variant is a strong candidate for a pathogenic variant. However, the possibility it may be a rare benign variant cannot be excluded.
GeneReviews RCV000239751 SCV000298199 pathogenic Early infantile epileptic encephalopathy 13 2016-02-19 no assertion criteria provided literature only

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