Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002394383 | SCV002701501 | uncertain significance | Cardiovascular phenotype | 2022-10-27 | criteria provided, single submitter | clinical testing | The p.T481I variant (also known as c.1442C>T), located in coding exon 8 of the TBX5 gene, results from a C to T substitution at nucleotide position 1442. The threonine at codon 481 is replaced by isoleucine, an amino acid with 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 |
RCV003103694 | SCV003246418 | uncertain significance | Aortic valve disease 2 | 2022-06-12 | criteria provided, single submitter | clinical testing | 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 has not been reported in the literature in individuals affected with TBX5-related conditions. This variant is present in population databases (rs772556634, gnomAD 0.003%). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 481 of the TBX5 protein (p.Thr481Ile). |