Total submissions: 4
| 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. |
| Labcorp Genetics |
RCV003114381 | SCV003787741 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2024-12-11 | 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 missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 37652022). 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. |
| All of Us Research Program, |
RCV003997737 | SCV004829329 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma | 2023-05-04 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with proline at codon 331 of the DSP protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 been identified in 1/251124 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. |
| Ambry Genetics | RCV004619228 | SCV005117173 | uncertain significance | Cardiovascular phenotype | 2024-06-13 | criteria provided, single submitter | clinical testing | The p.Q331P variant (also known as c.992A>C), located in coding exon 8 of the DSP gene, results from an A to C substitution at nucleotide position 992. The glutamine at codon 331 is replaced by proline, an amino acid with similar properties. This alteration has been reported in a dilated cardiomyopathy (DCM) cohort (Mazzarotto F et al. Circulation, 2020 Feb;141:387-398). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |