ClinVar Miner

Submissions for variant NM_001330260.2(SCN8A):c.5047G>A (p.Asp1683Asn)

dbSNP: rs1023188648
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001253575 SCV001369807 uncertain significance Developmental and epileptic encephalopathy, 13 2018-12-07 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2.
Institute of Human Genetics, University of Leipzig Medical Center RCV001253575 SCV001429365 uncertain significance Developmental and epileptic encephalopathy, 13 2019-08-21 criteria provided, single submitter clinical testing
Invitae RCV001321331 SCV001512156 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2023-12-21 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1683 of the SCN8A protein (p.Asp1683Asn). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN8A-related conditions. ClinVar contains an entry for this variant (Variation ID: 931859). 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 not expected to disrupt SCN8A protein function with a negative 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 RCV001561633 SCV001784267 uncertain significance not provided 2020-07-02 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); 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 (Stenson et al., 2014)

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