Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000181390 | SCV000233692 | uncertain significance | not provided | 2011-12-22 | criteria provided, single submitter | clinical testing | The Val2737Ala variant in the DSP gene has not been reported previously as a disease-causing mutation, nor as a benign polymorphism, to our knowledge. Although Val2737Ala results in a conservative substitution of one non-polar amino acid for another, the Val2737 residue is conserved across species. The NHLBI ESP Exome Variant Server reports Val2737Ala in 1/3,737 alleles from individuals of African American ancestry. However, no data from ethnically-matched controls are available to assess for a population-specific benign variant. In addition, few disease-causing missense mutations have been reported in this region of the DSP gene, indicating this region of the protein may tolerate change (Van der Zwaag PA et al., 2009). In summary, with the clinical and molecular information available at this time, we cannot determine whether the Val2737Ala variant is a disease-causing mutation or a rare benign variant. The variant is found in ARVC panel(s). |
| Invitae | RCV000791642 | SCV000930900 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 2737 of the DSP protein (p.Val2737Ala). This variant is not present in population databases (gnomAD no frequency). 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: 199941). 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. |