Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002553529 | SCV002157905 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2021-10-23 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RYR2 protein function. This variant has not been reported in the literature in individuals affected with RYR2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with alanine at codon 75 of the RYR2 protein (p.Val75Ala). The valine residue is moderately conserved and there is a small physicochemical difference between valine and alanine. |