Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000521599 | SCV000619830 | uncertain significance | not provided | 2017-08-08 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the DSP gene. The R1425K variant has been reported in one patient with anthracycline-associated cardiomyopathy (AACM) (Wasielewski et al., 2014). The R1425K variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). However, the R1425K variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is only conserved in mammals and where lysine (K) is present as the wild type in multiple species. In silico analysis suggests that this variant likely does not alter the protein structure/function. |
Color Diagnostics, |
RCV001185067 | SCV001351208 | uncertain significance | Cardiomyopathy | 2023-04-26 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with lysine at codon 1425 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 dilated cardiomyopathy (PMID: 25332820). This variant has been identified in 4/251366 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 | RCV002525196 | SCV003479277 | likely benign | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2024-01-04 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003302759 | SCV003996581 | uncertain significance | Cardiovascular phenotype | 2023-05-19 | criteria provided, single submitter | clinical testing | The p.R1425K variant (also known as c.4274G>A), located in coding exon 23 of the DSP gene, results from a G to A substitution at nucleotide position 4274. The arginine at codon 1425 is replaced by lysine, an amino acid with highly similar properties. This alteration has been reported in subjects with anthracycline-associated cardiomyopathy and dilated cardiomyopathy (DCM) (Wasielewski M et al. Open Heart, 2014 Jul;1:e000116; Mazzarotto F et al. Circulation, 2020 Feb;141:387-398). This variant was also detected in a cardiomyopathy genetic testing cohort; however, clinical details were limited, and additional cardiac variants were detected in some cases (van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309). This amino acid position is not 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. |
Ce |
RCV000521599 | SCV004703338 | uncertain significance | not provided | 2024-02-01 | criteria provided, single submitter | clinical testing | DSP: PM2, BP4 |