ClinVar Miner

Submissions for variant NM_001330260.2(SCN8A):c.4819G>A (p.Glu1607Lys)

dbSNP: rs1555230905
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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 RCV001377181 SCV001574440 likely pathogenic Early infantile epileptic encephalopathy with suppression bursts 2024-01-07 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1607 of the SCN8A protein (p.Glu1607Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of SCN8A-related conditions (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 1066236). 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 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.
GeneDx RCV001581111 SCV001812273 pathogenic not provided 2020-12-03 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Ambry Genetics RCV002341819 SCV002637888 uncertain significance Inborn genetic diseases 2019-05-14 criteria provided, single submitter clinical testing The p.E1607K variant (also known as c.4819G>A), located in coding exon 26 of the SCN8A gene, results from a G to A substitution at nucleotide position 4819. The glutamic acid at codon 1607 is replaced by lysine, an amino acid with similar properties. This variant has been determined to be the result of a de novo mutation or germline mosaicism in one family with an isolated case of epilepsy (Ambry internal data). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV001581111 SCV003821364 uncertain significance not provided 2019-08-03 criteria provided, single submitter clinical testing

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