Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000181153 | SCV000233430 | uncertain significance | not provided | 2014-01-02 | criteria provided, single submitter | clinical testing | p.Ser526Ala (TCA>GCA): c.1576 T>G in exon 11 of the DSC2 gene (NM_024422.3). he S526A variant in the DSC2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Although the S526A variant is a non-conservative amino acid substitution as these residues differ in polarity, charge, size and/or other properties and is more likely to impact secondary structure, the S526 residue is not well conserved across species. In silico analysis predicts S526A is benign to the protein structure/function. Furthermore, no missense mutations in nearby residues have been reported in association with ARVC, indicating this region of the protein may tolerate change. Nevertheless, the S526A 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. With the clinical and molecular information available at this time, we cannot definitively determine if S526A is a disease-causing mutation or a rare benign variant. This result cannot be interpreted for diagnosis or used for family member screening at this time. The variant is found in ARVC panel(s). |