Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000215746 | SCV000271736 | uncertain significance | not specified | 2015-04-16 | criteria provided, single submitter | clinical testing | The p.Ala2021Gly variant in DSP has not been previously reported in individuals with cardiomyopathy, but been identified in 1/66550 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Computation al prediction tools and conservation analysis suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p.Ala2021Gly varian t is uncertain. |
Gene |
RCV000766953 | SCV000571991 | uncertain significance | not provided | 2017-07-24 | criteria provided, single submitter | clinical testing | The A2021G variant of uncertain significance in the DSP gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A2021G variant of uncertain significance in the DSP gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at any significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A2021G variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Moreover, this substitution occurs at a position that is not conserved across species. Nevertheless, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |
Ambry Genetics | RCV000621984 | SCV000735860 | uncertain significance | Cardiovascular phenotype | 2023-05-09 | criteria provided, single submitter | clinical testing | The p.A2021G variant (also known as c.6062C>G), located in coding exon 24 of the DSP gene, results from a C to G substitution at nucleotide position 6062. The alanine at codon 2021 is replaced by glycine, an amino acid with similar properties. This alteration has been reported in a control cohort (Mazzarotto F et al. Circulation, 2020 Feb;141:387-398). 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. |
Invitae | RCV000641794 | SCV000763443 | likely benign | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2023-12-14 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV001187340 | SCV001354111 | uncertain significance | Cardiomyopathy | 2023-06-16 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with glycine at codon 2021 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 not been reported in individuals affected with DSP-related disorders in the literature, but has been reported in one individual in a healthy control population (PMID: 31983221). This variant has been identified in 7/282288 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. |