Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002552904 | SCV002147732 | pathogenic | Catecholaminergic polymorphic ventricular tachycardia 1 | 2021-08-06 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of RYR2-related conditions (Invitae). In at least one individual the variant was observed to be de novo. 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. For these reasons, this variant has been classified as Pathogenic. This sequence change replaces aspartic acid with glutamic acid at codon 2300 of the RYR2 protein (p.Asp2300Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. |