Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001379326 | SCV001577112 | likely pathogenic | Catecholaminergic polymorphic ventricular tachycardia | 2021-09-01 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV003225185 | SCV003921799 | pathogenic | Catecholaminergic polymorphic ventricular tachycardia 1 | 2021-05-06 | 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) (PMIDs: 12459180, 27646203, 29477366). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from tyrosine to cysteine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools and highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated ion transport domain (NCBI). (I) 0703 - Other missense variants comparable to the one identified in this case have moderate previous evidence for pathogenicity. Two alternative changes at the same residue, to asparagine and histidine, have previously been classified as likely pathogenic (ClinVar, LOVD). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. The variant has previously been reported in at least two individuals with catecholaminergic polymorphic ventricular tachycardia 1 (MIM#604772), one of whom was shown to be de novo (HGMD, PMIDs: 23595086, 26114861, 29434162, 29453246). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 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 |
| Gene |
RCV004699353 | SCV005201507 | likely pathogenic | not provided | 2024-01-29 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Located in one of the three hot-spot regions of the RYR2 gene, where the majority of pathogenic missense variants occur (PMID: 19926015); This variant is associated with the following publications: (PMID: 29434162, 19926015, 26114861, 35135837, 32152366, 34697415, 23595086) |