Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001364097 | SCV001560230 | uncertain significance | Epileptic encephalopathy | 2020-02-04 | criteria provided, single submitter | clinical testing | 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: "Benign"; Align-GVGD: "Class C0"). 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. This variant has not been reported in the literature in individuals with RYR3-related conditions. This variant is present in population databases (rs760619857, ExAC 0.001%). This sequence change replaces threonine with alanine at codon 235 of the RYR3 protein (p.Thr235Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. |