ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.3733C>T (p.Arg1245Ter) (rs727504136)

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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 RCV000188925 SCV000203500 pathogenic not provided 2014-02-20 criteria provided, single submitter clinical testing
Center for Bioinformatics, Peking University RCV000153888 SCV000221834 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
GeneDx RCV000188925 SCV000242555 pathogenic not provided 2019-04-26 criteria provided, single submitter clinical testing Nonsense variant predicted to result in nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 17054684, 21906962, 24168886, 25525159, 12821740, 22150645, 26096185, 31009440, 30945278, 31864146, 32090326, 31031587)
Athena Diagnostics Inc RCV000153888 SCV000255825 pathogenic Severe myoclonic epilepsy in infancy 2015-02-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV000720345 SCV000851222 pathogenic History of neurodevelopmental disorder 2016-09-15 criteria provided, single submitter clinical testing The p.R1245* pathogenic mutation (also known as c.3733C>T), located in coding exon 19 of the SCN1A gene, results from a C to T substitution at nucleotide position 3733. This changes the amino acid from an arginine to a stop codon within coding exon 19. This alteration has been reported in individuals with <span style="font-size:12px">severe myoclonic epilepsy of <span style="font-size:12px">infancy (SMEI) and Dravet syndrome. (Craig AK et al. Seizure, 2012 Jan;21:17-20; Nabbout R et al. Neurology, 2003 Jun;60:1961-7; Zhang Y et al. PLoS ONE, 2015 Nov;10:e0141782). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Invitae RCV001040173 SCV001203734 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2020-07-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1245*) in the SCN1A gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in individuals affected with early infantile epileptic encephalopathy (PMID: 12821740). ClinVar contains an entry for this variant (Variation ID: 167639). Loss-of-function variants in SCN1A are known to be pathogenic (PMID: 17347258, 18930999). For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000188925 SCV001247841 pathogenic not provided 2017-06-01 criteria provided, single submitter clinical testing

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