Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000697510 | SCV000826125 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2024-03-02 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 1412 of the SCN1A protein (p.Lys1412Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 575324). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SCN1A protein function with a positive predictive value of 95%. 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 | RCV002275118 | SCV002564180 | uncertain significance | Migraine, familial hemiplegic, 3; Severe myoclonic epilepsy in infancy; Generalized epilepsy with febrile seizures plus, type 2; Developmental and epileptic encephalopathy 6B | 2021-09-26 | criteria provided, single submitter | clinical testing | The heterozygous c.4201A>G (p.Lys1401Glu) missense variant identified in the SCN1A gene has not been reported in affected individuals in the literature. The variant is absent from gnomAD(v3) database suggesting it is not a common benign variant in the populations represented in that database. This variant has been reported in the ClinVar database as variant of uncertain significance [Variation ID: 575324]. The variant affects an evolutionarily conserved residue and is predicted deleterious by multiple in silico prediction tools (CADD score = 26.2, REVEL score = 0.950). Given the lack of functional studies and no reports of affected individuals in the literature/public repositories, the heterozygous c.4201A>G (p.Lys1401Glu) missense variant identified in the SCN1A gene is reported as a Variant of Uncertain Significance. |