ClinVar Miner

Submissions for variant NM_000192.3(TBX5):c.835C>T (p.Arg279Ter) (rs863223788)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre de Biologie Pathologie Génétique,Centre Hospitalier Universitaire de Lille RCV000782289 SCV000920808 pathogenic Holt-Oram syndrome 2018-06-14 no assertion criteria provided clinical testing
GeneDx 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).
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000782289 SCV000992546 pathogenic Holt-Oram syndrome 2019-03-20 criteria provided, single submitter research
Invitae RCV000459213 SCV000552104 pathogenic Aortic valve disease 2 2018-11-08 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.

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