ClinVar Miner

Submissions for variant NM_006920.6(SCN1A):c.4319C>T (p.Pro1440Leu) (rs121917945)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000812820 SCV000953146 pathogenic Early infantile epileptic encephalopathy 2018-11-16 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1451 of the SCN1A protein (p.Pro1451Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with severe myoclonic epilepsy in infancy (SMEI) also known as Dravet syndrome (PMID: 17054684). ClinVar contains an entry for this variant (Variation ID: 68544). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Pro1451 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 21248271, 26096185), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
NeuroMeGen,Hospital Clinico Santiago de Compostela RCV000059418 SCV000693759 likely pathogenic Severe myoclonic epilepsy in infancy 2018-01-01 criteria provided, single submitter clinical testing
UniProtKB/Swiss-Prot RCV000059418 SCV000090942 not provided Severe myoclonic epilepsy in infancy no assertion provided not provided

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