Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000170865 | SCV000223420 | uncertain significance | not provided | 2014-06-12 | criteria provided, single submitter | clinical testing | p.Ser167Leu (TCA>TTA): c.500 C>T in exon 5 of the CACNB2 gene (NM_000724.3). A variant of unknown significance has been identified in the CACNB2 gene. The S167L variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The S167L 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. Another missense mutation in a nearby residue (S160T) has been reported in association with early repolarization syndrome. The S167L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved when present across species. However, 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 mutation or a rare benign variant. The variant is found in ARRHYTHMIA panel(s). |
| Invitae | RCV001852045 | SCV002113669 | uncertain significance | Brugada syndrome 4 | 2023-05-19 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CACNB2 protein function. ClinVar contains an entry for this variant (Variation ID: 190723). This variant has not been reported in the literature in individuals affected with CACNB2-related conditions. This variant is present in population databases (rs761542420, gnomAD 0.006%). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 168 of the CACNB2 protein (p.Ser168Leu). |
| Ambry Genetics | RCV002336397 | SCV002640967 | uncertain significance | Cardiovascular phenotype | 2022-03-31 | criteria provided, single submitter | clinical testing | The p.S168L variant (also known as c.503C>T), located in coding exon 5 of the CACNB2 gene, results from a C to T substitution at nucleotide position 503. The serine at codon 168 is replaced by leucine, an amino acid with dissimilar properties. 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, |
RCV001852045 | SCV002776821 | uncertain significance | Brugada syndrome 4 | 2021-07-27 | criteria provided, single submitter | clinical testing |