Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000182852 | SCV000235240 | likely pathogenic | not provided | 2020-05-21 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Invitae | RCV002515339 | SCV000814925 | likely pathogenic | Catecholaminergic polymorphic ventricular tachycardia 1 | 2018-06-07 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 C0"). This variant has been observed to be de novo in an individual affected with RYR2-related disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 201363). This variant is not present in population databases (ExAC no frequency). This sequence change replaces tryptophan with arginine at codon 4949 of the RYR2 protein (p.Trp4949Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. |