ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.1841C>T (p.Pro614Leu)

gnomAD frequency: 0.00004  dbSNP: rs143734912
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766773 SCV000242878 uncertain significance not provided 2021-05-29 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; This substitution is predicted to be within the cytoplasmic loop between the first and second homologous domains; Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Genetic Services Laboratory, University of Chicago RCV000189246 SCV000596971 uncertain significance not specified 2017-04-13 criteria provided, single submitter clinical testing
Invitae RCV000640618 SCV000762212 uncertain significance Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2024-01-08 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 614 of the SCN2A protein (p.Pro614Leu). This variant is present in population databases (rs143734912, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of SCN2A-related conditions (PMID: 33004838). ClinVar contains an entry for this variant (Variation ID: 207091). 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 SCN2A protein function with a positive 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.

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