ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.4807G>T (p.Gly1603Ter) (rs761333438)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000525130 SCV000633865 likely pathogenic Early infantile epileptic encephalopathy 2017-02-14 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the second to last exon of the SCN1A mRNA at codon 1603 (p.Gly1603*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 407 amino acids of the SCN1A protein. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an SCN1A-related disease. Multiple missense substitutions (p.Arg1636Gln and p.Ser1773Tyr) contained within the deleted region of this variant have been determined to be pathogenic (PMID: 19589774, 17347258, Invitae database). This suggests that this deleted region contains amino acid residues that are critical for SCN1A protein function. In summary, this variant is a novel nonsense variant that that is expected to disrupt amino acid residues that are critical for SCN1A protein function. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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