Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001227407 | SCV001399766 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2020-01-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Lys1432 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with clinical features of early infantile epileptic encephalopathy (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with glutamic acid at codon 1432 of the SCN1A protein (p.Lys1432Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. |
| Ambry Genetics | RCV002327543 | SCV002626690 | uncertain significance | Inborn genetic diseases | 2018-04-24 | criteria provided, single submitter | clinical testing | The p.K1432E variant (also known as c.4294A>G), located in coding exon 22 of the SCN1A gene, results from an A to G substitution at nucleotide position 4294. The lysine at codon 1432 is replaced by glutamic acid, an amino acid with similar properties. Another variant affecting this codon has been detected in a Dravet syndrome cohort (Lee HF et al. Brain Dev., 2015 Jun;37:599-611). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |