Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000218147 | SCV000271748 | uncertain significance | not specified | 2015-12-14 | criteria provided, single submitter | clinical testing | The p.Gln331Pro variant in DSP has not been previously reported in individuals w ith cardiomyopathy but has been identified in 1/66616 of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP r s746517026). Computational prediction tools and conservation analysis suggest th at this variant may impact the protein, though this information is not predictiv e enough to determine pathogenicity. In summary, the clinical significance of th e p.Gln331Pro variant is uncertain. |
| Invitae | RCV003114381 | SCV003787741 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2023-12-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 331 of the DSP protein (p.Gln331Pro). This variant is present in population databases (rs746517026, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with DSP-related conditions. ClinVar contains an entry for this variant (Variation ID: 228654). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |