ClinVar Miner

Submissions for variant NM_006920.6(SCN1A):c.4873C>T (p.Arg1625Ter) (rs199727342)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000180823 SCV000255831 pathogenic Severe myoclonic epilepsy in infancy 2012-11-13 criteria provided, single submitter clinical testing
Center for Bioinformatics, Peking University RCV000180823 SCV000221787 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000188982 SCV000336787 pathogenic not provided 2015-11-06 criteria provided, single submitter clinical testing
GeneDx RCV000188982 SCV000242613 pathogenic not provided 2015-11-09 criteria provided, single submitter clinical testing p.Arg1636Stop (CGA>TGA): c.4906 C>T in exon 26 of the SCN1A gene (NM_001165963.1) The Arg1636Stop nonsense mutation in the SCN1A gene has been reported previously in a male patient with Dravet syndrome (Zuberi et al., 2011). This mutation is predicted to cause loss of normal protein function through protein truncation as the last 373 amino acids of the protein are lost. The variant is found in INFANT-EPI panel(s).
Invitae RCV000804066 SCV000943960 pathogenic Early infantile epileptic encephalopathy 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.

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