Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV000013826 | SCV005087145 | pathogenic | Catecholaminergic polymorphic ventricular tachycardia 1 | 2023-07-17 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Dominant negative and gain of function are known mechanisms of disease in this gene and are associated with catecholaminergic polymorphic ventricular tachycardia 1 (MIM#604772) and left ventricular non-compaction (PMIDs: 12459180, 27646203, 29477366, 31875585, 33500567). Loss of function has been reported for ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome (MIM#115000); however, a dominant negative mechanism has not been excluded (PMID: 33536282). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0112 - The condition associated with this gene has incomplete penetrance. Penetrance for CPVT is estimated to be 60-70% (PMID: 23549275). (I) 0200 - Variant is predicted to result in a missense amino acid change from proline to serine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2: 1 heterozygote, 0 homozygotes). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0602 - Variant is located in a hotspot region or cluster of pathogenic variants (PMID: 30696458). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. It has been found in at least four unrelated families with CPVT (PMIDs: 11157710, 15197150, 33315912). (SP) 0901 - This variant has strong evidence for segregation with disease. In a large family with 17 carriers, 10 out of 12 had exercise-induced ventricular tachycardia. In addition, two carriers were asymptomatic but displayed abnormal clinical findings (PMIDs: 11157710, 15197150). (SP) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| OMIM | RCV000013826 | SCV000034073 | pathogenic | Catecholaminergic polymorphic ventricular tachycardia 1 | 2004-06-29 | no assertion criteria provided | literature only | |
| Gene |
RCV000013826 | SCV000057859 | not provided | Catecholaminergic polymorphic ventricular tachycardia 1 | no assertion provided | literature only |