ClinVar Miner

Submissions for variant NM_006920.6(SCN1A):c.5189G>A (p.Cys1730Tyr) (rs794726763)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Bioinformatics, Peking University RCV000180878 SCV000221847 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
GeneDx RCV000188996 SCV000242627 pathogenic not provided 2013-05-03 criteria provided, single submitter clinical testing p.Cys1741Tyr (TGT>TAT): c.5222 G>A in exon 26 of the SCN1A gene (NM_001165963.1). The Cys1741Tyr 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. Although Cysteine and Tyrosine are both uncharged, polar amino acids, the loss of Cysteine residue may affected disulfide bond formation in the protein. Cys1741Tyr alters a highly conserved position in the pore loop between the S5 and S6 segments of the fourth transmembrane domain, and a different missense substitution at the same position (Cys1741Arg) was reported as a de novo mutation in a patient with Dravet syndrome (Wang et al., 2012). Additionally, multiple in silico algorithms predict Cys1741Tyr is damaging to protein structure/function. Therefore, Cys1741Tyr is considered a disease-causing mutation. The variant is found in EPILEPSY panel(s).

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