Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000232198 | SCV000288615 | uncertain significance | Atrial fibrillation, familial, 14 | 2016-03-01 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change with uncertain impact on protein function. 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 is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SCN2B-related disease. This sequence change replaces arginine with histidine at codon 137 of the SCN2B protein (p.Arg137His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. |
| Ambry Genetics | RCV002321873 | SCV002628020 | uncertain significance | Cardiovascular phenotype | 2021-11-19 | criteria provided, single submitter | clinical testing | The p.R137H variant (also known as c.410G>A), located in coding exon 3 of the SCN2B gene, results from a G to A substitution at nucleotide position 410. The arginine at codon 137 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |