Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Wendy Chung Laboratory, |
RCV000664179 | SCV000784738 | uncertain significance | Pulmonary arterial hypertension associated with congenital heart disease | 2018-06-27 | criteria provided, single submitter | case-control | |
Wendy Chung Laboratory, |
RCV001829825 | SCV002097198 | likely pathogenic | Pulmonary hypertension, primary, 1 | 2019-11-01 | criteria provided, single submitter | research | |
Labcorp Genetics |
RCV002530597 | SCV003483322 | pathogenic | not provided | 2022-09-22 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individuals with pulmonary arterial hypertension (PMID: 30029678, 30578397, 33066286). 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 creates a premature translational stop signal (p.Pro371Leufs*8) in the TBX4 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 175 amino acid(s) of the TBX4 protein. ClinVar contains an entry for this variant (Variation ID: 548694). For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the TBX4 protein in which other variant(s) (p.Arg389Glnfs*30) have been determined to be pathogenic (PMID: 15106123). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. |