Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000424004 | SCV000529416 | uncertain significance | not provided | 2016-07-06 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the DSP gene. The C1805Y variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The C1805Y variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The C1805Y variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Nevertheless, this substitution occurs at a position that is only conserved in mammals where Tyrosine is typical for multiple other species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |
| Invitae | RCV001042347 | SCV001206024 | likely benign | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2022-12-06 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV003532110 | SCV004363432 | uncertain significance | Cardiomyopathy | 2022-07-25 | criteria provided, single submitter | clinical testing | This missense variant replaces cysteine with tyrosine at codon 1805 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 7/251024 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. |