ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.913_915ACT[3] (p.Thr306dup) (rs1469280756)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189249 SCV000242881 uncertain significance not specified 2014-10-16 criteria provided, single submitter clinical testing The c.916_918dupACT variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The normal sequence with the duplicated bases in brackets: TACT[dupACT]TTCA. The c.916_918dupACT variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The c.916_918dupACT results in an in-frame duplication of a single Threonine residue at a poorly conserved position in the SCN2A protein and is not expected to result in protein truncation or nonsense-mediated mRNA decay. To our knowledge, in-frame duplications have not been previously reported in the SCN2A gene in association with epilepsy. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000734281 SCV000862409 uncertain significance not provided 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV001064654 SCV001229566 uncertain significance Benign familial neonatal-infantile seizures; Early infantile epileptic encephalopathy 11 2019-12-05 criteria provided, single submitter clinical testing This variant, c.916_918dup, results in the insertion of 1 amino acid(s) to the SCN2A protein (p.Thr306dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs762721688, ExAC 0.02%). This variant has not been reported in the literature in individuals with SCN2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 207094). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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