ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.1294G>C (p.Ala432Pro)

dbSNP: rs1697892980
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Inherited Metabolic Diseases, Karolinska University Hospital RCV001375628 SCV001572551 likely pathogenic Epilepsy 2021-04-25 criteria provided, single submitter clinical testing Variant inherited from a parent with childhood epilepsy and migraine. Patient seizures worsened by Lamotrigine. Seizures not febrile triggered
GeneDx RCV002466672 SCV002762486 pathogenic not provided 2022-12-07 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This substitution is predicted to be in the cytoplasmic loop between the first and second homologous domains; This variant is associated with the following publications: (PMID: 27236449)
Labcorp Genetics (formerly Invitae), Labcorp RCV003753178 SCV004373610 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2023-04-09 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 432 of the SCN1A protein (p.Ala432Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1065178). 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 SCN1A protein function. 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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