ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.4435C>A (p.Gln1479Lys)

dbSNP: rs1553462134
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000501194 SCV000596972 likely pathogenic Developmental and epileptic encephalopathy, 11 2017-06-14 criteria provided, single submitter clinical testing
Invitae RCV001865623 SCV002216817 uncertain significance Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2023-04-26 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 436661). 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. 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. This variant has not been reported in the literature in individuals affected with SCN2A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 1479 of the SCN2A protein (p.Gln1479Lys).
3billion RCV000501194 SCV002521336 likely pathogenic Developmental and epileptic encephalopathy, 11 2022-05-22 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.90; 3Cnet: 0.99). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with SCN2A related disorder (ClinVar ID: VCV000436661). However, the evidence of pathogenicity is insufficient at this time. A different missense change at the same codon (p.Gln1479His) has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV001180106, VCV001308640). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

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