ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.1624C>T (p.Arg542Ter)

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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 RCV000180802 SCV000221758 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
GeneDx RCV000188870 SCV000242500 pathogenic not provided 2018-05-21 criteria provided, single submitter clinical testing The Arg542Stop nonsense variant in the SCN1A gene has been reported previously in association with Dravet syndrome (Depienne et al., 2006). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
Invitae RCV000636424 SCV000757863 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2020-09-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg542*) 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 reported to be de novo in individuals affected with early infantile epileptic encephalopathy (PMID: 17054684). This variant has also been reported to segregate in families with early infantile epileptic encephalopathy or Dravet syndrome (PMID: 16541393, 20522430). ClinVar contains an entry for this variant (Variation ID: 189848). Loss-of-function variants in SCN1A are known to be pathogenic (PMID: 17347258, 18930999). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000718366 SCV000849228 pathogenic History of neurodevelopmental disorder 2018-05-08 criteria provided, single submitter clinical testing The p.R542* pathogenic mutation (also known as c.1624C>T), located in coding exon 10 of the SCN1A gene, results from a C to T substitution at nucleotide position 1624. This changes the amino acid from an arginine to a stop codon within coding exon 10. This mutation has been detected as a de novo occurrence in an individual with Dravet syndrome and in an individual with severe myoclonic epilepsy of infancy (SMEI) (Mancardi MM et al. Epilepsia, 2006 Oct;47:1629-35; Xu X et al. Brain Dev., 2014 Sep;36:676-81). In addition, in one family, this mutation was inherited from an unaffected mother in two siblings with Dravet syndrome. In this family, the mother was shown to have germline mosaicism for the mutation (Depienne C et al. Hum. Mutat., 2006 Apr;27:389). 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.
Génétique des Maladies du Développement, Hospices Civils de Lyon RCV001004730 SCV001164201 pathogenic Generalized epilepsy with febrile seizures plus, type 2 2018-04-16 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV001004730 SCV001428559 pathogenic Generalized epilepsy with febrile seizures plus, type 2 2018-01-17 criteria provided, single submitter clinical testing

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