ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.354G>T (p.Arg118Ser) (rs121917959)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000364532 SCV000330395 pathogenic not provided 2016-09-14 criteria provided, single submitter clinical testing An apparently de novo R118S pathogenic variant has been identified in the SCN1A gene. A different nucleotide substitution (c.354 G>C) resulting in the same amino acid substitution (R118S) has been reported previously as a de novo pathogenic variant in an individual with severe myoclonic epilepsy of infancy (Zucca et al., 2008). R118S 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 R118S variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Additionally, this substitution alters a highly conserved position predicted to be within the N-terminal domain of the SCN1A protein. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in a nearby residue (P113T) has been reported in the Human Gene Mutation Database in association with an SCN1A-related disorder (Stenson et al., 2014). Therefore, we now interpret R118S as a pathogenic variant.
Mendelics RCV000986918 SCV001136073 likely pathogenic Severe myoclonic epilepsy in infancy 2019-05-28 criteria provided, single submitter clinical testing

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