ClinVar Miner

Submissions for variant NM_001330260.2(SCN8A):c.1094G>A (p.Arg365His)

dbSNP: rs1592390511
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000796166 SCV000935665 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2023-06-10 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 365 of the SCN8A protein (p.Arg365His). 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. 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 SCN8A protein function. ClinVar contains an entry for this variant (Variation ID: 642664). This variant has not been reported in the literature in individuals affected with SCN8A-related conditions. This variant is not present in population databases (gnomAD no frequency).
Mendelics RCV002249508 SCV002519060 pathogenic Cognitive impairment with or without cerebellar ataxia 2022-05-04 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV003224880 SCV003921095 uncertain significance Developmental and epileptic encephalopathy, 13 2023-03-03 criteria provided, single submitter clinical testing _x000D_ Criteria applied: PS4_SUP, PM2_SUP, PP3
GeneDx RCV003328629 SCV004035572 uncertain significance not provided 2023-09-11 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This substitution is predicted to be within the pore forming loop between the S5 and S6 transmembrane segments of the first homologous domain; Missense variants in this gene are often considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 27535533)

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