Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000171672 | SCV000050699 | uncertain significance | not provided | 2013-06-24 | criteria provided, single submitter | research | |
Invitae | RCV002517655 | SCV000760612 | uncertain significance | Catecholaminergic polymorphic ventricular tachycardia 1 | 2021-08-12 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with glutamic acid at codon 503 of the RYR2 protein (p.Asp503Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. This variant is present in population databases (rs764532025, ExAC 0.002%). This missense change has been observed in individual(s) with sudden cardiac death (PMID: 30670673). ClinVar contains an entry for this variant (Variation ID: 191479). 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. 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. |
Color Diagnostics, |
RCV001191376 | SCV001359188 | uncertain significance | Cardiomyopathy | 2023-05-10 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with glutamic acid at codon 503 of the RYR2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with sudden arrhythmia death syndrome (PMID: 30670673). This variant has also been reported in an individual affected with arrhythmogenic right ventricular cardiomyopathy and in an affected family member (PMID: 32660257). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |