ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.4906C>T (p.Arg1636Ter) (rs199727342)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Bioinformatics, Peking University RCV000180823 SCV000221787 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
GeneDx RCV000188982 SCV000242613 pathogenic not provided 2019-05-31 criteria provided, single submitter clinical testing Reported as pathogenic in ClinVar but additional evidence is not available (ClinVar Variant ID#: 189870; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 374 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 26467025, 21248271, 28202706, 21868258, 30034362, 29655203, 32090326, 33278787, 31031587)
Athena Diagnostics Inc RCV000180823 SCV000255831 pathogenic Severe myoclonic epilepsy in infancy 2012-11-13 criteria provided, single submitter clinical testing
Eurofins NTD, LLC RCV000188982 SCV000336787 pathogenic not provided 2015-11-06 criteria provided, single submitter clinical testing
Invitae RCV000804066 SCV000943960 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2018-08-15 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SCN1A gene (p.Arg1636*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 374 amino acids of the SCN1A protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with classic or borderline Dravet syndrome (PMID: 1868258, 21248271, 28202706) amongst whom in one individual it is reported as de novo (PMID: 21868258) . ClinVar contains an entry for this variant (Variation ID: 189870). A different truncation (p.Arg1886*) that lies downstream of this variant has been determined to be pathogenic (PMID: 17054684, 18930999, Invitae). This suggests that deletion of this region of the SCN1A protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000188982 SCV001245866 pathogenic not provided 2021-04-01 criteria provided, single submitter clinical testing

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