Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001189691 | SCV001357038 | uncertain significance | Cardiomyopathy | 2023-05-19 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with leucine at codon 908 of the DSP protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with arrhythmogenic cardiomyopathy (PMID: 33652588). This variant has been identified in 4/251322 chromosomes 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. |
| Invitae | RCV001212971 | SCV001384583 | likely benign | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2023-11-24 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003380868 | SCV004088816 | uncertain significance | Cardiovascular phenotype | 2023-07-11 | criteria provided, single submitter | clinical testing | The p.R908L variant (also known as c.2723G>T), located in coding exon 19 of the DSP gene, results from a G to T substitution at nucleotide position 2723. The arginine at codon 908 is replaced by leucine, an amino acid with dissimilar properties. This alteration has been reported in a sudden cardiac arrest cohort and an arrhythmogenic right ventricular cardiomyopathy (ARVC) cohort (Asatryan B et al. Am J Cardiol, 2019 Jun;123:2031-2038; Vallverdú-Prats M et al. J Pers Med, 2021 Feb;11:). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |