Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000128812 | SCV000322019 | uncertain significance | not provided | 2017-12-14 | criteria provided, single submitter | clinical testing | The V54G variant in the SCN3B gene has been reported in one individual with idiopathic ventricular fibrillation and also in this individual's asymptomatic mother (Valdivia C et al., 2010). In addition, the V54G variant has been reported in one case of SIDS and was absent from 800 control alleles (Tan B et al., 2010). Furthermore, the V54G variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Moreover, in vitro functional studies show that the V54G variant causes loss of channel function (Valdivia et al., 2010; Tan et al., 2010). However, the V54G variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is where amino acids with similar properties to Valine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Labcorp Genetics |
RCV001243331 | SCV001416481 | uncertain significance | Brugada syndrome 7 | 2019-10-09 | 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. This variant has been reported to affect SCN3B protein function (PMID: 20042427, 20226894). This variant has been observed in an individual affected with ventricular fibrillation (PMID: 20042427) and in an individual who suffered sudden unexplained death (PMID: 20226894). ClinVar contains an entry for this variant (Variation ID: 140596). This variant is present in population databases (rs587777555, ExAC 0.003%). This sequence change replaces valine with glycine at codon 54 of the SCN3B protein (p.Val54Gly). The valine residue is highly conserved and there is a moderate physicochemical difference between valine and glycine. |
| Ambry Genetics | RCV002399507 | SCV002708029 | uncertain significance | Cardiovascular phenotype | 2022-11-20 | criteria provided, single submitter | clinical testing | The p.V54G variant (also known as c.161T>G), located in coding exon 2 of the SCN3B gene, results from a T to G substitution at nucleotide position 161. The valine at codon 54 is replaced by glycine, an amino acid with dissimilar properties. This variant has been reported in an individual with idiopathic ventricular fibrillation and in a sudden infant death case (Valdivia CR et al. Cardiovasc. Res., 2010 Jun;86:392-400; Tan BH et al. Heart Rhythm, 2010 Jun;7:771-8). Limited in vitro studies by these authors suggest that this alteration may impact protein function; however, the clinical implications of these findings are unknown. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV001243331 | SCV002791298 | uncertain significance | Brugada syndrome 7 | 2021-08-31 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000128812 | SCV000172470 | uncertain significance | not provided | 2010-06-01 | no assertion criteria provided | literature only |