Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001226468 | SCV001398782 | uncertain significance | Epileptic encephalopathy | 2022-01-15 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. ClinVar contains an entry for this variant (Variation ID: 954077). This variant has not been reported in the literature in individuals affected with RYR3-related conditions. This variant is present in population databases (rs201466342, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2594 of the RYR3 protein (p.Ala2594Val). |