ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.1076A>G (p.Asn359Ser) (rs794726713)

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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 RCV000180817 SCV000221781 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000329798 SCV000340111 uncertain significance not provided 2016-04-01 criteria provided, single submitter clinical testing
Invitae RCV001377988 SCV001575453 likely pathogenic Early infantile epileptic encephalopathy with suppression bursts 2020-06-30 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 359 of the SCN1A protein (p.Asn359Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of, or diagnosis of, SCN1A-related conditions (PMID: 21248271, 29056246, 29655203). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 189864). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C1). This variant disrupts the p.Asn359 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been observed in individuals with SCN1A-related conditions (PMID: 29142202, 23808377, 23708187), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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