Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000824359 | SCV000965255 | uncertain significance | Atrial fibrillation, familial, 14 | 2023-08-04 | 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. Experimental studies have shown that this missense change affects SCN2B function (PMID: 23559163, 28597987). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 60776). This missense change has been observed in individual(s) with Brugada syndrome (PMID: 23559163). This variant is present in population databases (rs587777023, gnomAD 0.002%). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 211 of the SCN2B protein (p.Asp211Gly). |
| Ambry Genetics | RCV002354244 | SCV002654584 | uncertain significance | Cardiovascular phenotype | 2019-08-19 | criteria provided, single submitter | clinical testing | The p.D211G variant (also known as c.632A>G), located in coding exon 4 of the SCN2B gene, results from an A to G substitution at nucleotide position 632. The aspartic acid at codon 211 is replaced by glycine, an amino acid with similar properties. This alteration was reported in a subject with Brugada syndrome, but was also seen in family members with nonspecific symptoms or who were unaffected (Riuró H et al. Hum. Mutat., 2013 Jul;34:961-6). This alteration may have an impact in protein function (Riuró H et al. Hum. Mutat., 2013 Jul;34:961-6; Dulsat G et al. Biol. Cell, 2017 Jul;109:273-291). This amino acid position is not well conserved in available vertebrate species, and glycine 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. |
| OMIM | RCV000054543 | SCV000083021 | uncertain significance | Variant of unknown significance | 2013-07-01 | no assertion criteria provided | literature only |