ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.3956G>A (p.Arg1319Gln) (rs121917753)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189142 SCV000242774 pathogenic not provided 2018-08-28 criteria provided, single submitter clinical testing The R1319Q missense variant has been previously published in multiple unrelated families with benign familial neonatal-infantile seizures (BFNIS) and benign familial infantile seizures (BFIS) (Berkovic et al., 2004; Zara et al., 2013). The R1319Q variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R1319Q missense change is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution alters a highly conserved position predicted to be within the transmembrane segment S4 voltage sensor of the third homologous domain, and functional studies indicate it results in a loss of Nav1.2 channel function (Misra et al., 2008). Therefore, the presence of R1319Q is consistent with the diagnosis of an SCN2A-related disorder in this individual.
OMIM RCV000013740 SCV000033987 pathogenic Benign familial neonatal-infantile seizures 2004-04-01 no assertion criteria provided literature only

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