ClinVar Miner

Submissions for variant NM_001165963.1(SCN1A):c.769T>C (p.Cys257Arg) (rs794726771)

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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 RCV000180887 SCV000221856 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
GeneDx RCV000188845 SCV000242475 likely pathogenic not provided 2018-08-21 criteria provided, single submitter clinical testing p.Cys257Arg (TGT>CGT): c.769 T>C in exon 6 of the SCN1A gene (NM_001165963.1) The Cys257Arg 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 an uncharged Cysteine residue is replaced by a positively charged Arginine residue, and the loss of a Cysteine may affect disulfide bond formation in the protein. It alters a highly conserved position in the S5 segment of the first transmembrane domain of the protein, and multiple in silico algorithms predict it may be damaging to protein structure/function. Therefore, based on the currently available information, Cys257Arg is a strong candidate for a disease-causing mutation, although the possibility that it is a benign variant cannot be excluded. The variant is found in EPILEPSY panel(s).

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