Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000232378 | SCV000289894 | uncertain significance | Arrhythmogenic right ventricular dysplasia 13 | 2023-12-13 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 71 of the CTNNA3 protein (p.Asp71Glu). This variant is present in population databases (rs771791661, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with CTNNA3-related conditions. ClinVar contains an entry for this variant (Variation ID: 240868). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CTNNA3 protein function with a negative predictive value of 80%. 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. |
| Ambry Genetics | RCV002429126 | SCV002730066 | uncertain significance | Inborn genetic diseases | 2022-03-25 | criteria provided, single submitter | clinical testing | The p.D71E variant (also known as c.213C>G), located in coding exon 2 of the CTNNA3 gene, results from a C to G substitution at nucleotide position 213. The aspartic acid at codon 71 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |