Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000618198 | SCV000734882 | uncertain significance | Cardiovascular phenotype | 2016-06-10 | criteria provided, single submitter | clinical testing | The c.9128+5delA intronic variant is located 5 nucleotides after coding exon 64 of the RYR2 gene. This variant results from a deletion of the nucleotide at position c.9128+5. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 5838 samples (11676 alleles) with coverage at this position. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
| Invitae | RCV002528810 | SCV001542398 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2020-06-26 | 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. 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 is not likely to affect RNA splicing, 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. ClinVar contains an entry for this variant (Variation ID: 518465). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 64 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. |