ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.4913T>A (p.Ile1638Asn)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000417978 SCV000520960 likely pathogenic not provided 2017-03-21 criteria provided, single submitter clinical testing A I1638N variant that is likely pathogenic has been identified in the SCN1A gene. The I1638N variant has been reported previously as a de novo variant in an individual with severe myoclonic epilepsy of infancy (Wang et al., 2012). The I1638N variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The I1638N variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution alters a conserved position predicted to be within the transmembrane segment S4 voltage sensor of the fourth homologous domain. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (R1636Q, V1637E, R1639G, R1642S) have been reported in the Human Gene Mutation Database in association with SCN1A-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Génétique des Maladies du Développement, Hospices Civils de Lyon RCV001004732 SCV001164203 pathogenic Generalized epilepsy with febrile seizures plus, type 2 2018-06-25 criteria provided, single submitter clinical testing

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