Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001177814 | SCV001342086 | uncertain significance | Cardiomyopathy | 2020-01-24 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with isoleucine at codon 249 of the PKP2 protein. Computational prediction tool is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. 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. |
Fulgent Genetics, |
RCV002483966 | SCV002785948 | uncertain significance | Arrhythmogenic right ventricular dysplasia 9 | 2021-08-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002483966 | SCV003031145 | uncertain significance | Arrhythmogenic right ventricular dysplasia 9 | 2022-06-07 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 249 of the PKP2 protein (p.Ser249Ile). 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: 919574). This variant has not been reported in the literature in individuals affected with PKP2-related conditions. This variant is not present in population databases (gnomAD no frequency). |