Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002403267 | SCV002709321 | uncertain significance | Cardiovascular phenotype | 2022-07-14 | criteria provided, single submitter | clinical testing | The p.D516N variant (also known as c.1546G>A), located in coding exon 8 of the TBX5 gene, results from a G to A substitution at nucleotide position 1546. The aspartic acid at codon 516 is replaced by asparagine, 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. |
| Labcorp Genetics |
RCV003096906 | SCV003280930 | uncertain significance | Aortic valve disease 2 | 2022-01-11 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with TBX5-related conditions. 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. 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 TBX5 protein function. This variant is present in population databases (rs200354838, gnomAD 0.003%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 516 of the TBX5 protein (p.Asp516Asn). |