Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001962276 | SCV002136742 | uncertain significance | DiGeorge syndrome | 2021-11-01 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with TBX1-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 proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 374 of the TBX1 protein (p.Pro374His). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). |
| Ambry Genetics | RCV002440945 | SCV002748604 | uncertain significance | Cardiovascular phenotype | 2022-03-21 | criteria provided, single submitter | clinical testing | The p.P374H variant (also known as c.1121C>A), located in coding exon 8 of the TBX1 gene, results from a C to A substitution at nucleotide position 1121. The proline at codon 374 is replaced by histidine, an amino acid with similar properties. This amino acid position is conserved. 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. |