ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.2876G>A (p.Cys959Tyr) (rs794726716)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Bioinformatics, Peking University RCV000180820 SCV000221784 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
GeneDx RCV000256008 SCV000321939 pathogenic not provided 2016-06-16 criteria provided, single submitter clinical testing The C959Y variant has been previously reported as a de novo variant in an individual withLennox-Gastaut syndrome (Allen et al., 2013). It was not observed in approximately 6,500individuals of European and African American ancestry in the NHLBI Exome Sequencing Project,indicating it is not a common benign variant in these populations. The C959Y variant is anon-conservative amino acid substitution, which is likely to impact secondary protein structure asthese residues differ in polarity, charge, size and/or other properties. This substitution occurs at aconserved position predicted to be within the pore forming loop between the S5 and S6transmembrane segments of the 2nd homologous domain. A different missense variant at the sameposition (C959R) as well as multiple missense variants in nearby residues have been reported inthe Human Gene Mutation Database in association with SCN1A-related disorders (Stenson et al.,2014), supporting the functional importance of this region of the protein.
Mayo Clinic Laboratories, Mayo Clinic RCV000256008 SCV001714609 pathogenic not provided 2019-08-12 criteria provided, single submitter clinical testing PS2, PM1, PM2, PM5, PP3

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