Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002544844 | SCV000817110 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2023-11-28 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 3891 of the RYR2 protein (p.Tyr3891Phe). This variant is present in population databases (no rsID available, gnomAD no frequency). This missense change has been observed in individual(s) with catecholaminergic polymorphic ventricular tachycardia (PMID: 31112425). ClinVar contains an entry for this variant (Variation ID: 568949). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available". The phenylalanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Fulgent Genetics, |
RCV002507196 | SCV002816539 | uncertain significance | Arrhythmogenic right ventricular dysplasia 2; Catecholaminergic polymorphic ventricular tachycardia 1; Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome | 2021-10-13 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV003532230 | SCV004361499 | uncertain significance | Cardiomyopathy | 2023-03-21 | criteria provided, single submitter | clinical testing | This missense variant replaces tyrosine with phenylalanine at codon 3891 of the RYR2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with sudden death (PMID: 27810088). Two first-degree relatives of this proband were carriers of this variant and unaffected with RYR2-related disorders . This variant has been identified in 1/248152 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |