Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000693716 | SCV000821597 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2023-11-08 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1566 of the SCN1A protein (p.Ser1566Asn). This variant is present in population databases (rs200263247, gnomAD 0.009%). 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: 572354). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SCN1A protein function. 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. |
| Ambry Genetics | RCV002315994 | SCV000847616 | uncertain significance | Inborn genetic diseases | 2016-08-29 | criteria provided, single submitter | clinical testing | The p.S1566N variant (also known as c.4697G>A), located in coding exon 25 of the SCN1A gene, results from a G to A substitution at nucleotide position 4697. The serine at codon 1566 is replaced by asparagine, an amino acid with highly similar properties. This variant was previously reported in the SNPDatabase as rs200263247. Based on data from the 1000 Genomes Project, the A allele has an overall frequency of approximately 0.05% (1/2098) total alleles studied. The highest observed frequency was 0.86% (1/116) Mexican-American alleles. In the NHLBI Exome Sequencing Project (ESP), this variant was not observed in 6503 samples with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |