Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002567946 | SCV001413169 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2019-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 3943 of the RYR2 protein (p.Ala3943Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs762237329, ExAC 0.009%). This variant has been observed in an individual affected with sudden unexplained death (PMID: 24631775). 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. 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. |