Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002533476 | SCV000825750 | likely pathogenic | Catecholaminergic polymorphic ventricular tachycardia 1 | 2018-06-08 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed to be de novo in individuals affected with catecholaminergic polymorphic ventricular tachycardia (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with glutamic acid at codon 3955 of the RYR2 protein (p.Gln3955Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. |