ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.5734C>T (p.Arg1912Ter) (rs77216276)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000586829 SCV000697773 pathogenic Autosomal dominant epilepsy 2016-02-03 criteria provided, single submitter clinical testing Variant summary: SCN1A c.5734C>T variant results in a premature termination codon, predicted to cause a truncated or absent SCN1A protein, which is a commonly known mechanism for SCN1A-related seizure disorders. Mutation Taster predicts a damaging outcome for this variant, but functional studies have not been carried out to confirm this prediction. This variant is found in 1/121470 control chromosomes at a frequency of 0.0000082, which does not significantly exceed maximal expected frequency of a pathogenic allele (0.0000179). However, the variant has been identified in multiple affected patients in the literature as a de novo mutation, and also as a paternally inherited variant from an asymptomatic mosaic father. Taken together, this is a disease variant and was classified as pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001090356 SCV001245857 pathogenic not provided 2017-08-01 criteria provided, single submitter clinical testing
Invitae RCV001223212 SCV001395351 pathogenic Early infantile epileptic encephalopathy 2019-06-20 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SCN1A gene (p.Arg1912*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 98 amino acids of the SCN1A protein. This variant is present in population databases (rs77216276, ExAC 0.001%). This variant has been observed in individuals affected with Dravet syndrome (PMID: 14738421, 23195492, Invitae), including an individual who inherited the variant from an unaffected mosaic parent (PMID: 20522430) . This variant is also known as R1902X in the literature. ClinVar contains an entry for this variant (Variation ID: 496124). For these reasons, this variant has been classified as Pathogenic.

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