ClinVar Miner

Submissions for variant NM_006920.6(SCN1A):c.4901G>A (p.Arg1634Gln) (rs121917976)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000720127 SCV000851004 pathogenic History of neurodevelopmental disorder 2016-05-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Confirmed de novo alteration in the setting of a new disease (appropriate phenotype) in the family,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Structural Evidence,Other strong data supporting pathogenic classification
Fulgent Genetics,Fulgent Genetics RCV000763457 SCV000894234 pathogenic Familial hemiplegic migraine type 3; Severe myoclonic epilepsy in infancy; Generalized epilepsy with febrile seizures plus, type 2 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000188986 SCV000242617 pathogenic not provided 2018-05-02 criteria provided, single submitter clinical testing The R1645Q missense variant in the SCN1A gene has been reported previously as a de novo variant in association with Dravet syndrome (also called severe myoclonic epilepsy of infancy or SMEI) (Berkovic et al., 2006; Harkin et al., 2007; Bolszak et al., 2009; Parrini et al., 2017). The R1645Q variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The R1645Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Additionally, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Furthermore, missense variants in nearby residues have been reported in the Human Gene Mutation Database in individuals with SCN1A-related disorders (Stenson et al., 2014). This substitution is predicted to be within the transmembrane segment S4 voltage sensor of the fourth homologous domain. Therefore, the presence of R1645Q is consistent with the diagnosis of an SCN1A-related disorder in this individual.
Neurogenetics Laboratory - MEYER,AOU Meyer RCV000059432 SCV000494514 pathogenic Severe myoclonic epilepsy in infancy 2016-11-16 criteria provided, single submitter clinical testing
UniProtKB/Swiss-Prot RCV000059432 SCV000090956 not provided Severe myoclonic epilepsy in infancy no assertion provided not provided

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