Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002532267 | SCV000822928 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-07-06 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 250 of the CASQ2 protein (p.Arg250Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with catecholaminergic polymorphic ventricular tachycardia (PMID: 30600839). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 572954). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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. |
| Ambry Genetics | RCV002388254 | SCV002669815 | likely pathogenic | Cardiovascular phenotype | 2022-04-26 | criteria provided, single submitter | clinical testing | The p.R250C variant (also known as c.748C>T), located in coding exon 7 of the CASQ2 gene, results from a C to T substitution at nucleotide position 748. The arginine at codon 250 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant has been reported in a family with three affected siblings with catecholaminergic polymorphic ventricular tachycardia (CPVT) and a CASQ2 nonsense variant in trans, as well as in their unaffected carrier mother (Gao L et al. Cardiol J, 2018;25:756-758). This variant was also detected in an exome cohort, but clinical details were not provided (Landstrom AP et al. Circ Arrhythm Electrophysiol, 2017 Apr;10:[Epub ahead of print]). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Fulgent Genetics, |
RCV002485675 | SCV002797698 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1; Catecholaminergic polymorphic ventricular tachycardia 2 | 2021-09-10 | criteria provided, single submitter | clinical testing | |
| Breakthrough Genomics, |
RCV004691282 | SCV005186843 | uncertain significance | not provided | criteria provided, single submitter | not provided |