ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.5506G>T (p.Glu1836Ter) (rs1064795579)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483871 SCV000571528 likely pathogenic not provided 2016-08-30 criteria provided, single submitter clinical testing The E1836X variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The E1836X likely pathogenic variant is predicted to cause loss of normal protein function through protein truncation, as the last 174 amino acids of the SCN1A protein are lost. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Invitae RCV001232515 SCV001405077 pathogenic Early infantile epileptic encephalopathy 2019-07-29 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SCN1A gene (p.Glu1836*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 174 amino acids of the SCN1A protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SCN1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 422136). This variant disrupts the C-terminus of the SCN1A protein. Other variant(s) that disrupt this region (p.Arg1912*) have been determined to be pathogenic (PMID: 14738421, 23195492, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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