ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.5735G>A (p.Arg1912Gln)

gnomAD frequency: 0.00001  dbSNP: rs373896263
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000806199 SCV000946185 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2023-11-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1912 of the SCN1A protein (p.Arg1912Gln). This variant is present in population databases (rs373896263, gnomAD 0.002%). 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: 650943). 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.
Ambry Genetics RCV001266647 SCV001444823 uncertain significance Inborn genetic diseases 2019-09-08 criteria provided, single submitter clinical testing
Centre for Inherited Metabolic Diseases, Karolinska University Hospital RCV001375624 SCV001572546 uncertain significance Generalized epilepsy with febrile seizures plus, type 2 2021-04-25 criteria provided, single submitter clinical testing Considered to be causative of the patients phenotype. The father is also a carrier and he had febrile seizures.
GeneDx RCV001585733 SCV001819356 uncertain significance not provided 2023-10-16 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign in association with epilepsy to our knowledge; Not observed at a significant frequency in large population cohorts (gnomAD); This substitution is predicted to be within the C-terminal cytoplasmic domain.; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 33726816)

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