Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001905411 | SCV002134125 | uncertain significance | Aortic valve disease 2 | 2021-06-28 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with threonine at codon 159 of the TBX5 protein (p.Lys159Thr). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and threonine. This variant has not been reported in the literature in individuals 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 expected to disrupt TBX5 protein function. |