ClinVar Miner

Submissions for variant NM_003239.4(TGFB3):c.442C>T (p.Arg148Ter) (rs1057523647)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000436458 SCV000532858 likely pathogenic not provided 2017-06-28 criteria provided, single submitter clinical testing A likely pathogenic variant has been identified in the TGFB3 gene. The R148X variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This 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. The R148X variant is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Furthermore, other nonsense variants in the TGFB3 gene have been reported in the Human Gene Mutation Database in association with aortic aneurysm and dissection (Stenson et al., 2014).In summary, R148X in the TGFB3 gene is expected to be pathogenic, as loss of function variants in this gene are strongly associated with this phenotype.
Ambry Genetics RCV000617852 SCV000739733 uncertain significance Cardiovascular phenotype 2017-05-02 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000817993 SCV000958581 pathogenic Loeys-Dietz syndrome 4 2018-10-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg148*) in the TGFB3 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with clinical features of TGFB3-related disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 390113). Loss-of-function variants in TGFB3 are known to be pathogenic (PMID: 25835445, 26188975). For these reasons, this variant has been classified as Pathogenic.

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