Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001324465 | SCV001515419 | uncertain significance | Epileptic encephalopathy | 2020-12-22 | criteria provided, single submitter | clinical testing | 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. 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 C0"). This variant has not been reported in the literature in individuals with RYR3-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with serine at codon 3965 of the RYR3 protein (p.Cys3965Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine. |
| New York Genome Center | RCV001780248 | SCV002025679 | uncertain significance | See cases | 2020-05-07 | criteria provided, single submitter | clinical testing | The inherited c.11894G>C,p.Cys3965Ser variant has not been reported in the literature in individuals with RYR3-related conditions. The variant has 0.0008% allele frequency in the gnomAD database (2 out of 249,122 heterozygous alleles), indicating this is a rare allele. In silico tool predicts the variant is expected to be deleterious [PMID: 24681721]. Based on the available evidence, the variant c.11894G>C, p.Cys3965Ser in the RYR3 gene is classified as Variant of Uncertain Significance. |