Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000182884 | SCV000235272 | uncertain significance | not provided | 2017-08-17 | criteria provided, single submitter | clinical testing | This variant is denoted Ala3342Pro (aka A3342P) at the protein level and c.10024 G>C at the cDNA level. The Ala3342Pro variant in the RYR2 gene has not been reported previously as a disease-causing mutation or as a benign polymorphism, to our knowledge. Ala3342Pro results in a conservative amino acid substitution of one non-polar amino acid for another at a position that is not well conserved across species throughout evolution. In addition, no mutations in nearby residues have been reported in association with CPVT, indicating this region of the protein may be tolerant of change. However, according to the NHLBI ESP Exome Variant Server, Ala3342Pro was not observed in approximately 4,500 individuals from European and African American backgrounds, indicating that it is not a common sequence variant in these populations. In summary, the clinical significance of the Ala3342Pro variant is unclear at this time. The variant is found in CPVT panel(s). |
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV001256910 | SCV001433424 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2019-08-29 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001256910 | SCV003524139 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2022-09-03 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 201394). This missense change has been observed in individual(s) with idiopathic cardiac arrest (PMID: 28600387). This variant is present in population databases (rs779445295, gnomAD 0.0009%). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 3342 of the RYR2 protein (p.Ala3342Pro). |