ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.4907G>A (p.Arg1636Gln) (rs121917995)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000176634 SCV000228322 likely pathogenic not provided 2015-03-13 criteria provided, single submitter clinical testing
Invitae RCV000463147 SCV000548769 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2018-12-10 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1636 of the SCN1A protein (p.Arg1636Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with Lennox-Gastaut syndrome (PMID: 17347258, 19589774) and has been observed in individuals with seizures or early infantile epileptic encephalopathy (PMID: 26633542, Invitae). ClinVar contains an entry for this variant (Variation ID: 68557). 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 identified in the SCN1A gene is located in the transmembrane spanning D4-S4 region of the resulting protein (PMID: 25348405, 18804930), but it is unclear how this variant impacts the function of this protein. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000623263 SCV000743065 likely pathogenic Inborn genetic diseases 2017-10-23 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000176634 SCV001245865 pathogenic not provided 2016-08-01 criteria provided, single submitter clinical testing
UniProtKB/Swiss-Prot RCV000059431 SCV000090955 not provided Epileptic encephalopathy Lennox-Gastaut type no assertion provided not provided

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