Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000181296 | SCV000233587 | uncertain significance | not provided | 2014-08-20 | criteria provided, single submitter | clinical testing | p.Asp728His (GAT>CAT): c.2182 G>C in exon 16 of the DSP gene (NM_004415.2). A variant of unknown significance has been identified in the DSP gene. The D728H variant has not been published as a mutation or been reported as a benign polymorphism to our knowledge. The D728H variant was not observed in approximately 6,500 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 D728H 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. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, no missense mutations in nearby residues have been reported in association with familial arrhythmia. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in ARRHYTHMIA panel(s). |
| All of Us Research Program, |
RCV004806170 | SCV005428848 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma | 2024-05-14 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with histidine at codon 728 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. This variant has not been identified 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. |