Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Integrated Genetics/Laboratory Corporation of America | RCV000781828 | SCV000920176 | uncertain significance | not specified | 2017-09-15 | criteria provided, single submitter | clinical testing | Variant summary: The RYR2 c.9129-2A>G variant involves the alteration of a conserved intronic nucleotide. MutationTaster predicts a damaging outcome for this variant. 5/5 splice prediction tools predict a significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant is absent in 168162 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories, nor evaluated for functional impact by in vivo/vitro studies. However, based on evaluation of other variants reported in disease databases such as HGMD and ClinVar, the vast majority of variants in patients are missense; splice site and truncating variants (i.e., loss of function) are not typically found in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) or cardiomyopathy. Because of the absence of clinical information, the lack of functional studies, and the unclear association of splice site variants with cardiac abnormalities in this gene, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available. |