ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.1339A>G (p.Met447Val)

dbSNP: rs777596738
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188868 SCV000242498 uncertain significance not provided 2024-11-12 criteria provided, single submitter clinical testing 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; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This substitution is predicted to be within the cytoplasmic loop between the first and second homologous domains
Labcorp Genetics (formerly Invitae), Labcorp RCV002514041 SCV003026548 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2024-04-27 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 447 of the SCN1A protein (p.Met447Val). This variant is present in population databases (rs777596738, gnomAD 0.01%). 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: 206765). 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 with a negative predictive value of 95%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Revvity Omics, Revvity RCV000188868 SCV003820742 uncertain significance not provided 2019-07-02 criteria provided, single submitter clinical testing

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