Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000540787 | SCV000641283 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2023-11-11 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 11 of the DSP gene. It does not directly change the encoded amino acid sequence of the DSP protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with DSP-related conditions. ClinVar contains an entry for this variant (Variation ID: 465881). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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, |
RCV001805175 | SCV002051990 | uncertain significance | Cardiomyopathy | 2023-10-02 | criteria provided, single submitter | clinical testing | This variant causes a G to C nucleotide substitution at the +5 position of intron 11 of the DSP gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing, however, this prediction has not been confirmed in published RNA studies. 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. |
| Ambry Genetics | RCV002395387 | SCV002698539 | uncertain significance | Cardiovascular phenotype | 2023-03-07 | criteria provided, single submitter | clinical testing | The c.1419+5G>C intronic variant results from a G to C substitution 5 nucleotides after coding exon 11 in the DSP gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| All of Us Research Program, |
RCV003999165 | SCV004837538 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma | 2024-08-06 | criteria provided, single submitter | clinical testing | This variant causes a G to C nucleotide substitution at the +5 position of intron 11 of the DSP gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing, however, this prediction has not been confirmed in published RNA studies. 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. |