Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000794018 | SCV000933400 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2018-09-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with lysine at codon 1728 of the DSP protein (p.Arg1728Lys). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and lysine. This variant is present in population databases (rs750854585, ExAC 0.006%). This variant has not been reported in the literature in individuals with DSP-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25". The lysine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Color Diagnostics, |
RCV001184159 | SCV001350076 | uncertain significance | Cardiomyopathy | 2023-04-25 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with lysine at codon 1728 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 4/251354 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. |