Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center For Human Genetics And Laboratory Diagnostics, |
RCV001089536 | SCV001244890 | likely pathogenic | Catecholaminergic polymorphic ventricular tachycardia 1 | 2019-10-20 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002393349 | SCV002697065 | uncertain significance | Cardiovascular phenotype | 2017-04-18 | criteria provided, single submitter | clinical testing | The p.I4926T variant (also known as c.14777T>C), located in coding exon 104 of the RYR2 gene, results from a T to C substitution at nucleotide position 14777. The isoleucine at codon 4926 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001089536 | SCV004273315 | pathogenic | Catecholaminergic polymorphic ventricular tachycardia 1 | 2023-07-07 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 4926 of the RYR2 protein (p.Ile4926Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with catecholaminergic polymorphic ventricular tachycardia (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 869441). 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. |