Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000472431 | SCV000548696 | uncertain significance | Atrial fibrillation, familial, 14 | 2022-06-04 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 408876). This variant has not been reported in the literature in individuals affected with SCN2B-related conditions. This variant is present in population databases (rs760669515, gnomAD 0.03%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 84 of the SCN2B protein (p.Arg84Cys). |
| Ambry Genetics | RCV002436428 | SCV002745132 | uncertain significance | Cardiovascular phenotype | 2020-07-28 | criteria provided, single submitter | clinical testing | The p.R84C variant (also known as c.250C>T), located in coding exon 3 of the SCN2B gene, results from a C to T substitution at nucleotide position 250. The arginine at codon 84 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration was detected by whole exome sequencing in an individual with sudden cardiac arrest due to idiopathic ventricular fibrillation. This individual also carried missense alterations in ANK2 (c.9689C>T p.Thr3230Met), CTNNA3 (c.1853A>G p.His618Arg), and TCAP (c.145G>A p.Glu49Lys) (Song JS et al. J. Hum. Genet., 2017 Jun;62:615-620). This amino acid position is well conserved in available 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. |