ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.3718_3729del (p.Ile1240_Asp1243del) (rs1574052546)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000797770 SCV000937349 uncertain significance Early infantile epileptic encephalopathy 2018-08-14 criteria provided, single submitter clinical testing This variant, c.3718_3729delATATATATTGAT, results in the deletion of 4 amino acids of the SCN1A protein (p.Ile1240_Asp1243del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with early infantile epileptic encephalopathy (Invitae). This variant identified in the SCN1A gene is located in the extracellular D3-S1/S2 region of the resulting protein (PMID: 25348405, 18804930), but it is unclear how this variant impacts the function of this protein. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. The observation of one or more variants affecting p.Tyr1241 (p.Tyr1241His and p.Ile1240_Asp1243del) in affected individuals suggests that this may be a clinically significant residue (PMID: 28012175, Invitae). 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.
New York Genome Center RCV001255048 SCV001431139 uncertain significance Global developmental delay; Seizures 2019-12-13 no assertion criteria provided clinical testing The c.3718_3729del (p.Ile1240_Asp1243del) variant identified is a small deletion that removes 12 nucleotides (4 amino acids) within exon 22/29 which preserves the reading frame of the transcript.This variant is also referred to as c.3685_3696del (p.Ile1229_Asp1232del) in the SCN1A transcript NM_006920.6. This region is well conserved and this variant is absent from gnomAD, suggesting it is not a common benign variant in the populations represented in this database. This variant is reported in ClinVar as a Variant of Uncertain Significance (VarID:643952), and is reported there by a clinical lab as being observed in an individual affected with early infantile epileptic encephalopathy. To our current knowledge this variant has not been reported in affected individuals in the literature.

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