ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.5632G>C (p.Glu1878Gln) (rs148703212)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766785 SCV000590382 uncertain significance not provided 2017-06-09 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCN1A gene. The E1878Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E1878Q variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The E1878Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Genetic Services Laboratory,University of Chicago RCV000497883 SCV000596944 uncertain significance not specified 2015-08-10 criteria provided, single submitter clinical testing
Invitae RCV001066109 SCV001231106 uncertain significance Early infantile epileptic encephalopathy 2019-11-26 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glutamine at codon 1878 of the SCN1A protein (p.Glu1878Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. This variant is present in population databases (rs148703212, ExAC 0.003%). This variant has not been reported in the literature in individuals with SCN1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 432633). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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