Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001314864 | SCV001505414 | uncertain significance | Epileptic encephalopathy | 2020-06-06 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs749924697, ExAC 0.003%). This sequence change replaces glutamic acid with aspartic acid at codon 1895 of the RYR3 protein (p.Glu1895Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant has not been reported in the literature in individuals with RYR3-related conditions. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. |