Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000362788 | SCV000330455 | pathogenic | not provided | 2016-05-05 | criteria provided, single submitter | clinical testing | The R429X pathogenic variant in the TBX18 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function through protein truncation. The R429X variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret R429X as a pathogenic variant |
| Diagnostics Services |
RCV000362788 | SCV001161702 | uncertain significance | not provided | 2020-01-23 | criteria provided, single submitter | clinical testing | TBX18 gene is thought to be responsible for the development of the myocytes in the ventricular septum and the atrial and ventricular walls of the heart. Congenital heart defects were reported earlier in patients with deletions involvingTBX18 gene (6q14.3) [Engwerda et al., Eur J Hum Genet 2018]. Heterozygous variants within the TBX18 gene promoter were reported in 4 individuals with ventricular septal defect, while no functional variants were found in a control group [Ma et al., Mol Cell Biochem 2013]. TBX18 also plays critical roles in limb development of vertebrates [Sheeba et al., Curr Top Dev Biol 2017]. Heterozygous variations in TBX18 gene are also known to cause congenital anomalies of kidney and urinary tract 2 (MIM#143400). The c.1285C>T variant is not present in publicly available databases like 1000 Genomes, Exome Variant Server (EVS), Exome Aggregation Consortium (ExAC) and Genome Aggregation Database (gnomAD). The variant is also not present in our in-house exome database. The variant was earlier reported as pathogenic in ClinVar database (Accession ID: VCV000280531.2), however, the phenotype or disease condition was not provided. This variant is predicted to cause loss of normal protein function through protein truncation. In-silico pathogenicity prediction programs MutationTaster2, CADD etc. predicted this variant as likely deleterious. This variant is being classified as uncertain significance in view of the clinical features reported in the patient. |