Submissions for variant NM_001165963.4(SCN1A):c.314C>A (p.Thr105Asn)

gnomAD frequency: 0.00001  dbSNP: rs796053089

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003103167	SCV003243202	uncertain significance	Early infantile epileptic encephalopathy with suppression bursts	2024-07-05	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 105 of the SCN1A protein (p.Thr105Asn). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1801821). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SCN1A protein function with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV004721075	SCV005326585	uncertain significance	not provided	2023-12-29	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This substitution is predicted to be within the N-terminal cytoplasmic domain.; Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; Has not been previously published as pathogenic or benign to our knowledge
Institute of Human Genetics, University of Goettingen	RCV002463978	SCV002754498	likely pathogenic	Severe myoclonic epilepsy in infancy	2022-11-24	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004736171	SCV005365349	uncertain significance	SCN1A-related disorder	2024-08-26	no assertion criteria provided	clinical testing	The SCN1A c.314C>A variant is predicted to result in the amino acid substitution p.Thr105Asn. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.