ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.302G>A (p.Arg101Gln) (rs121917918)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000188829 SCV000111453 pathogenic not provided 2015-09-11 criteria provided, single submitter clinical testing
Center for Bioinformatics, Peking University RCV000059400 SCV000221968 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
GeneDx RCV000188829 SCV000242458 pathogenic not provided 2016-09-06 criteria provided, single submitter clinical testing p.Arg101Gln (CGG>CAG): c.302 G>A in exon 2 of the SCN1A gene (NM_001165963.1) The R101Q mutation in the SCN1A gene has been reported previously as a de novo mutation in association with Dravet syndrome and other SCN1A-related disorders (Fukuma et al., 2004; Harkin et al., 2007; Depienne et al., 2009). It alters a highly conserved position in the N-terminal region of the protein, and another missense mutation at the same codon (R101W) has also been published in association with SCN1A-related disorders in an external mutation database. R101Q is non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Therefore, the presence of R101Q is consistent with a diagnosis of an SCN1A-related disorder. The variant is found in CHILD-EPI panel(s).
Invitae RCV000550639 SCV000633844 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2017-03-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 101 of the SCN1A protein (p.Arg101Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant has been shown to arise as de novo in multiple individuals with  Dravet syndrome (PMID: 24328833, 23808377, 23195492) and it has been shown to be inherited from mosaic parents (PMID: 14738421, 25986186). ClinVar contains an entry for this variant (Variation ID: 68528). A different missense substitution at this codon (p.Arg101Trp) has been determined to be pathogenic (PMID: 20431604, 23195492). This suggests that the arginine residue is critical for SCN1A protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000188829 SCV001249711 pathogenic not provided 2017-06-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001197275 SCV001367912 pathogenic Familial hemiplegic migraine type 3 2019-05-07 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PP3,PM1,PP2.
UniProtKB/Swiss-Prot RCV000059400 SCV000090924 not provided Severe myoclonic epilepsy in infancy no assertion provided not provided

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