Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
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 |
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, |
RCV000770948 | SCV000854410 | uncertain significance | Aortic valve disease 1 | 2018-11-14 | no assertion criteria provided | research |