Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002546969 | SCV001536663 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2020-06-16 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with RYR2-related conditions. This sequence change falls in intron 88 of the RYR2 gene. It does not directly change the encoded amino acid sequence of the RYR2 protein, but it affects a nucleotide within the consensus splice site of the intron. |
| Ambry Genetics | RCV002341703 | SCV002635767 | uncertain significance | Cardiovascular phenotype | 2018-12-10 | criteria provided, single submitter | clinical testing | The c.11880+3_11880+6delAAAC intronic variant, located in intron 88 of the RYR2 gene, results from a deletion of 4 nucleotides at positions c.11880+3 to c.11880+6. These nucleotide positions are not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |