ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.3389A>C (p.Glu1130Ala)

gnomAD frequency: 0.00001  dbSNP: rs1160491617
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000762289 SCV000892588 uncertain significance not provided 2018-04-01 criteria provided, single submitter clinical testing
Invitae RCV001202848 SCV001373979 uncertain significance Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2022-03-19 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 1130 of the SCN2A protein (p.Glu1130Ala). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 624155). This variant has not been reported in the literature in individuals affected with SCN2A-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%).
GeneDx RCV000762289 SCV002007506 uncertain significance not provided 2019-11-20 criteria provided, single submitter clinical testing Not observed at a significant frequency 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, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This substitution is predicted to be in the cytoplasmic loop between the second and third homologous domains (Shi et al., 2012); Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002458371 SCV002614568 uncertain significance Inborn genetic diseases 2017-07-26 criteria provided, single submitter clinical testing The p.E1130A variant (also known as c.3389A>C), located in coding exon 16 of the SCN2A gene, results from an A to C substitution at nucleotide position 3389. The glutamic acid at codon 1130 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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