Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000617189 | SCV000737681 | uncertain significance | Cardiovascular phenotype | 2022-11-17 | criteria provided, single submitter | clinical testing | The p.T13K variant (also known as c.38C>A), located in coding exon 1 of the TBX5 gene, results from a C to A substitution at nucleotide position 38. The threonine at codon 13 is replaced by lysine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002483716 | SCV002781800 | uncertain significance | Holt-Oram syndrome | 2021-10-09 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV002483716 | SCV003835496 | uncertain significance | Holt-Oram syndrome | 2022-09-10 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003647793 | SCV004536556 | uncertain significance | Aortic valve disease 2 | 2023-08-30 | 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. ClinVar contains an entry for this variant (Variation ID: 519312). This variant has not been reported in the literature in individuals affected with TBX5-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 13 of the TBX5 protein (p.Thr13Lys). |