Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000171058 | SCV000223622 | uncertain significance | not provided | 2022-08-29 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |
| Labcorp Genetics |
RCV000693228 | SCV000821088 | uncertain significance | Brugada syndrome 5 | 2024-01-03 | criteria provided, single submitter | clinical testing | The SCN1B gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_001037.5, and corresponds to NM_199037.4:c.*5584G>A in the primary transcript. This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 213 of the SCN1B protein (p.Gly213Asp). This variant is present in population databases (rs201209882, gnomAD 0.003%). This missense change has been observed in individual(s) with SCN1B-related conditions (PMID: 34034907). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 | RCV002354423 | SCV002655437 | uncertain significance | Cardiovascular phenotype | 2022-01-31 | criteria provided, single submitter | clinical testing | The p.G213D variant (also known as c.638G>A), located in coding exon 5 of the SCN1B gene, results from a G to A substitution at nucleotide position 638. The glycine at codon 213 is replaced by aspartic acid, an amino acid with similar properties. This variant was detected in both cases and controls in a pediatric epilepsy cohort; however, details were limited (Orrico A et al. Clin Genet, 2009 Jun;75:579-81). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the supporting evidence, the clinical significance of this variant for cardiac arrhythmia and autosomal recessive SCN1B-related early infantile epileptic encephalopathy is unclear; however, due to its observed frequencies in various cohorts, this variant is unlikely to be causative of autosomal dominant SCN1B-related epilepsy. |