Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001064912 | SCV001229848 | uncertain significance | DiGeorge syndrome | 2024-08-20 | criteria provided, single submitter | clinical testing | This variant, c.1122_1123insAGGGCCGGC, results in the insertion of 3 amino acid(s) of the TBX1 protein (p.Pro374_Gly375insArgAlaGly), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with TBX1-related conditions (Invitae). This variant has been observed in at least one individual who was not affected with TBX1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 858922). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| New York Genome Center | RCV002265935 | SCV002548634 | uncertain significance | Conotruncal heart malformations; Velocardiofacial syndrome; DiGeorge syndrome; Tetralogy of Fallot | 2021-05-21 | criteria provided, single submitter | clinical testing | The inherited c.1122_1123insAGGGCCGGC (p.Pro374_Gly375insArgAlaGly) variant identified in the TBX1 gene is the insertion of 9 nucleotides, which is predicted to lead to the in-frame insertion of 3 amino acids, Arginine, Alanine, Glycine, at amino acid 374-375/496. This variant is absent from gnomAD(v3.1.1) suggesting it is not a common benign variant in the populations represented in that database, although other in-frame insertions and deletions are present in this region. The c.1122_1123insAGGGCCGGC (p.Pro374_Gly375insArgAlaGly) variant is reported in ClinVar as a Variant of Uncertain Significance (VarID:858922) and to our current knowledge has not been reported in affected individuals in the literature. The p.Pro374-Gly375 residues are not within a mapped domain of TBX1 (UniProtKB:O43435). Given the lack of compelling evidence for its pathogenicity, the inherited c.1122_1123insAGGGCCGGC (p.Pro374_Gly375insArgAlaGly) variant identified in the TBX1 gene is reported as a Variant of Uncertain Significance. |