Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003104163 | SCV002294724 | likely pathogenic | Catecholaminergic polymorphic ventricular tachycardia 1 | 2024-01-16 | criteria provided, single submitter | clinical testing | This variant results in a copy number gain of the genomic region encompassing exon(s) 1-4 of the RYR2 gene. This region includes the initiator codon of the gene. The 5' end of this event is unknown as it extends beyond the assayed region for this gene and therefore may encompass additional genes. The 3' boundary is likely confined to intron 4 of the RYR2 gene. Although the duplication was reported as likely in tandem (PMID: 31913406), the exact location of this variant in the genome is unknown and it may be in tandem or it may be located elsewhere in the genome. A similar copy number variant has been observed in individual(s) with exercise-associated ventricular fibrillation (PMID: 31913406). Familial testing in Amish families indicates the affected relatives are homozygous for a duplication of exons 1-4 in RYR2. Homozygous individuals have experienced sudden death due to suspected ventricular fibrillation or resuscitated cardiac arrest. Heterozygous relatives with a single duplication of exons 1-4 (copy number = 3) are clinically unaffected without identifiable cardiac abnormalities. The Gain (exons 1-4), copy number = 4 has only been reported in Amish families to date, the risk of arrhythmia in individuals who are not of Amish ancestry is unknown. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |