Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002554615 | SCV001236306 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2019-12-04 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). This variant has not been reported in the literature in individuals with RYR2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with lysine at codon 190 of the RYR2 protein (p.Arg190Lys). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and lysine. |
Ambry Genetics | RCV002554614 | SCV003613723 | uncertain significance | Inborn genetic diseases | 2022-05-10 | criteria provided, single submitter | clinical testing | The c.569G>A (p.R190K) alteration is located in exon 8 (coding exon 8) of the RYR2 gene. This alteration results from a G to A substitution at nucleotide position 569, causing the arginine (R) at amino acid position 190 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |