ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.1289A>C (p.Glu430Ala) (rs796053183)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189209 SCV000242841 pathogenic not provided 2013-05-07 criteria provided, single submitter clinical testing p.Glu430Ala (GAA>GCA): c.1289 A>C in exon 10 of the SCN2A gene (NM_021007.2). The Glu430Ala missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. 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. The amino acid substitution is non-conservative, as a negatively charged Glutamic acid residue is replaced by an uncharged, non-polar Alanine residue. It alters a highly conserved position in the cytoplasmic loop between the first and second transmembrane domains, and multiple in silico algorithms predict Glu430Ala is likely damaging to protein structure/function. A different amino acid substitution at the same position, Glu430Gln, was previously identified in a large family with benign familial neonatal-infantile seizures (BFNIS) and was not detected in 88 control individuals (Herlenius et al., 2007). Therefore, based on the currently available information, Glu430Ala is considered a disease-causing mutation. The variant is found in EPILEPSY panel(s).

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