Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000797770 | SCV000937349 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2023-07-14 | criteria provided, single submitter | clinical testing | This variant has been observed in individual(s) with early infantile epileptic encephalopathy (Invitae). This variant, c.3718_3729del, results in the deletion of 4 amino acid(s) of the SCN1A protein (p.Ile1240_Asp1243del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 643952). This variant disrupts a region of the SCN1A protein in which other variant(s) (p.Tyr1241His) have been determined to be pathogenic (PMID: 28012175). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002345764 | SCV002619534 | uncertain significance | Inborn genetic diseases | 2018-01-18 | criteria provided, single submitter | clinical testing | The c.3718_3729del12 variant (also known as p.I1240_D1243del) is located in coding exon 19 of the SCN1A gene. This variant results from an in-frame ATATATATTGAT deletion at nucleotide positions 3718 to 3729. This results in the in-frame deletion of four amino acids between codons 1240 and 1243. These amino acid positions are well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al., PLoS ONE 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| New York Genome Center | RCV001255048 | SCV001431139 | uncertain significance | Global developmental delay; Seizure | 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. |