Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001946196 | SCV002215526 | pathogenic | Aortic valve disease 2 | 2021-09-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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. This missense change has been observed in individual(s) with clinical features of Holt-Oram syndrome (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with serine at codon 231 of the TBX5 protein (p.Pro231Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. |
| Ambry Genetics | RCV003375472 | SCV004096252 | uncertain significance | Cardiovascular phenotype | 2023-08-25 | criteria provided, single submitter | clinical testing | The p.P231S variant (also known as c.691C>T), located in coding exon 6 of the TBX5 gene, results from a C to T substitution at nucleotide position 691. The proline at codon 231 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |