Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000619379 | SCV000734917 | uncertain significance | Cardiovascular phenotype | 2024-08-31 | criteria provided, single submitter | clinical testing | The p.R1302H variant (also known as c.3905G>A), located in coding exon 23 of the DSP gene, results from a G to A substitution at nucleotide position 3905. The arginine at codon 1302 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, histidine is the reference amino acid in other vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001035533 | SCV001198862 | likely benign | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2023-04-26 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV001181382 | SCV001346519 | uncertain significance | Cardiomyopathy | 2020-12-09 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with histidine at codon 1302 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 cardiovascular disorders in the literature. This variant has been identified in 10/250814 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001194042 | SCV001363286 | uncertain significance | not specified | 2019-08-26 | criteria provided, single submitter | clinical testing | Variant summary: DSP c.3905G>A (p.Arg1302His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 250814 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in DSP causing Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (4e-05 vs 0.0002), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.3905G>A in individuals affected with Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| All of Us Research Program, |
RCV004807037 | SCV005428913 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma | 2024-04-10 | criteria provided, single submitter | clinical testing |