Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003811721 | SCV004616761 | uncertain significance | Aortic valve disease 2 | 2023-10-04 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 372 of the TBX5 protein (p.Ser372Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TBX5-related conditions. 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. 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 | RCV004673982 | SCV005168721 | uncertain significance | Cardiovascular phenotype | 2024-05-11 | criteria provided, single submitter | clinical testing | The p.S372T variant (also known as c.1114T>A), located in coding exon 8 of the TBX5 gene, results from a T to A substitution at nucleotide position 1114. The serine at codon 372 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |