Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001307751 | SCV001497176 | uncertain significance | Brugada syndrome 4 | 2021-08-25 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with tyrosine at codon 326 of the CACNB2 protein (p.His326Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CACNB2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. |
| Ambry Genetics | RCV004034138 | SCV005031996 | uncertain significance | Cardiovascular phenotype | 2023-01-18 | criteria provided, single submitter | clinical testing | The p.H326Y variant (also known as c.976C>T), located in coding exon 10 of the CACNB2 gene, results from a C to T substitution at nucleotide position 976. The histidine at codon 326 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |