Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588624 | SCV000698444 | uncertain significance | not provided | 2017-06-26 | criteria provided, single submitter | clinical testing | Variant summary: The DSP c.6566G>A (p.Arg2189Gln) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 4/121402 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.000288 (3/10406). This frequency is about 12 times the estimated maximal expected allele frequency of a pathogenic DSP variant (0.000025), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. However, the possibility of sublinical cardiac disease in the ExAC cohort of 4 individuals cannot be excluded . The variant has been reported in the literature in one arrythmia patient, without strong evidence for causality. The variant has not, to our knowledge, been reported by databases or reputable clinical labs. Taken together, this variant is classified as VUS-possibly benign. |
| Invitae | RCV000707496 | SCV000836596 | benign | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2023-12-31 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV001178829 | SCV001343373 | uncertain significance | Cardiomyopathy | 2023-03-31 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glutamine at codon 2189 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 arrhythmia (PMID: 26688388) and in an individual affected with left ventricular hypertrabeculation (PMID: 28798025). This variant has been identified in 9/282868 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. |
| Ambry Genetics | RCV002367993 | SCV002665276 | uncertain significance | Cardiovascular phenotype | 2021-11-09 | criteria provided, single submitter | clinical testing | The p.R2189Q variant (also known as c.6566G>A), located in coding exon 24 of the DSP gene, results from a G to A substitution at nucleotide position 6566. The arginine at codon 2189 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in a cardiac genetic testing cohort with limited clinical details and an additional alteration in a different cardiac-related gene, as well as in an individual with left ventricular hypertrabeculation (Chanavat V et al. Clin Chim Acta, 2016 Jan;453:80-5; Miszalski-Jamka K et al. Circ Cardiovasc Genet, 2017 Aug;10:). 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. |