ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.5719_5721ACT[2] (p.Thr1909del) (rs1553519902)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000636425 SCV000757864 likely pathogenic Early infantile epileptic encephalopathy 2018-01-28 criteria provided, single submitter clinical testing This variant, c.5725_5727delACT, results in the deletion of 1 amino acid of the SCN1A protein (p.Thr1909del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with severe myoclonic epilepsy of infancy syndrome (PMID: 21248271). It has also been found in another individual with generalized epilepsy (PMID: 28102150). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. Two different missense substitutions at this codon (p.Thr1909Ile, p.Thr1909Ala) have been reported in an individual with severe myoclonic epilepsy of infancy syndrome and determined to be pathogenic (PMID: 12083760, 17054685) and to be de novo in another individual with focal epilepsy (PMID: 28202706). This suggests that the threonine residue is critical for SCN1A protein function and that other change at this position may also be pathogenic. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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