ClinVar Miner

Submissions for variant NM_001321120.2(TBX4):c.702+1G>A

dbSNP: rs1555883342
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mayo Clinic Laboratories, Mayo Clinic RCV000660521 SCV000782622 pathogenic not provided 2017-01-18 criteria provided, single submitter clinical testing
Wendy Chung Laboratory, Columbia University Medical Center RCV000664178 SCV000784737 uncertain significance Pulmonary arterial hypertension associated with congenital heart disease 2018-06-27 criteria provided, single submitter case-control
Wendy Chung Laboratory, Columbia University Medical Center RCV001829824 SCV002097214 likely pathogenic Pulmonary hypertension, primary, 1 2019-11-01 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV000660521 SCV002122667 pathogenic not provided 2023-04-09 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 547941). Disruption of this splice site has been observed in individuals with pulmonary arterial hypertension (PMID: 29631995, 30029678). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 5 of the TBX4 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TBX4 are known to be pathogenic (PMID: 15106123, 31151956, 31761294, 31965066, 32079640).
PreventionGenetics, part of Exact Sciences RCV004547833 SCV004102905 pathogenic TBX4-related disorder 2023-09-15 criteria provided, single submitter clinical testing The TBX4 c.702+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant has been reported in individuals with pulmonary arterial hypertension and/or small patella syndrome (Table S1, Zhu et al. 2018. PubMed ID: 29631995; Table S2, Zhu et al. 2018. PubMed ID: 30029678; Table S2, Klee et al. 2020. PubMed ID: 33144682). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Variants that disrupt the consensus splice donor site in TBX4 are expected to be pathogenic. This variant is interpreted as pathogenic.

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