ClinVar Miner

Submissions for variant NM_001077653.2(TBX20):c.374C>A (p.Ser125Ter)

dbSNP: rs766692577
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002272337 SCV002557841 likely pathogenic Atrial septal defect 4 2023-07-17 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0103 - Loss of function and gain of function are known mechanisms of disease in this gene and are associated with atrial septal defect 4 (MIM#611363). Loss of function is associated with null and missense variants while gain of function has been reported for missense variants (PMIDs: 27642787, 19762328). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0703 - Other NMD-predicted variants comparable to the one identified in this case have moderate previous evidence for pathogenicity (ClinVar; PMIDs: 27510170, 28553164). (SP) 0803 - This variant has limited previous evidence of pathogenicity in unrelated individuals. This variant has been reported once in a study of individuals with bicuspid aortic valve/thoracic aortic aneurysm (PMID: 30820038). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1206 - This variant has been shown to be paternally inherited. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Labcorp Genetics (formerly Invitae), Labcorp RCV005092123 SCV005832073 pathogenic not provided 2024-08-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser125*) in the TBX20 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TBX20 are known to be pathogenic (PMID: 15901664, 25625280, 26118961, 27510170). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of TBX20-related conditions (PMID: 30820038). ClinVar contains an entry for this variant (Variation ID: 590957). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.
Centre of Medical Genetics, University of Antwerp RCV000770948 SCV000854410 uncertain significance Aortic valve disease 1 2018-11-14 no assertion criteria provided research

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