Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000196593 | SCV000250830 | pathogenic | not provided | 2018-02-19 | criteria provided, single submitter | clinical testing | The R279X nonsense variant in the TBX5 gene has been frequently reported in association with Holt-Oram syndrome (Heinritz et al., 2005; Brassington et al., 2003; Li et al., 1997). It is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In vitro studies on cardiac tissue harboring R279X show significantly decreased TBX5 transcript levels compared to wild type (Baban et al., 2014). |
Invitae | RCV000459213 | SCV000552104 | pathogenic | Aortic valve disease 2 | 2019-11-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal at codon 279 (p.Arg279*) of the TBX5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TBX5 are known to be pathogenic. This particular variant has been reported in the literature in several individuals affected with Holt-Oram syndrome (HOS) and Tetralogy of Fallot (TOF) (PMID: 21637475, 24664498, 25263169). ClinVar contains an entry for this variant (Variation ID: 213832). For these reasons, this variant has been classified as Pathogenic. |
Hudson |
RCV000782289 | SCV000992546 | pathogenic | Holt-Oram syndrome | 2019-06-14 | criteria provided, single submitter | research | ACMG codes: PVS1, PM2, PP4, PP5 |
Ce |
RCV000196593 | SCV001247477 | pathogenic | not provided | 2018-06-01 | criteria provided, single submitter | clinical testing | |
Centre de Biologie Pathologie Génétique, |
RCV000782289 | SCV000920808 | pathogenic | Holt-Oram syndrome | 2018-06-14 | no assertion criteria provided | clinical testing |