Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002362359 | SCV002661470 | uncertain significance | Cardiovascular phenotype | 2022-11-02 | criteria provided, single submitter | clinical testing | The c.691-5T>A intronic variant results from a T to A substitution 5 nucleotides upstream from coding exon 7 in the DSG2 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003098417 | SCV002971559 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2022-05-11 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 6 of the DSG2 gene. It does not directly change the encoded amino acid sequence of the DSG2 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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, |
RCV003533195 | SCV004363170 | uncertain significance | Cardiomyopathy | 2023-01-03 | criteria provided, single submitter | clinical testing | This variant causes a T to A nucleotide substitution at the -5 position of intron 6 of the DSG2 gene. Splice site prediction tools suggest that this variant may have a significant impact on RNA splicing, although this prediction has not been confirmed in published RNA studies. This variant has not been reported in individuals affected with DSG2-related 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. |
| All of Us Research Program, |
RCV004808289 | SCV005428681 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2024-03-05 | criteria provided, single submitter | clinical testing |