Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000646748 | SCV000768533 | uncertain significance | Brugada syndrome 5 | 2019-03-26 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SCN1B-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with threonine at codon 154 of the SCN1B protein (p.Met154Thr). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and threonine. The SCN1B gene has multiple clinically relevant transcripts. The p.Met154Thr variant occurs in alternate transcript NM_001037.4, which corresponds to c.*5031T>C in NM_199037.3, the primary transcript listed in the Methods. |
Gene |
RCV001584490 | SCV001820757 | uncertain significance | not provided | 2019-12-10 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002331208 | SCV002633399 | uncertain significance | Cardiovascular phenotype | 2018-04-02 | criteria provided, single submitter | clinical testing | The p.M154T variant (also known as c.461T>C), located in coding exon 4 of the SCN1B gene, results from a T to C substitution at nucleotide position 461. The methionine at codon 154 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and threonine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |