Description
The c.1333_1354dup22 likely pathogenic variant in the TBX1 gene causes a frameshift starting with codon Proline 452, changes this amino acid to an Arginine residue and creates an extended Stop codon at position 172 of the new reading frame, denoted p.Pro452ArgfsX172. While the variant abolishes part of the transactivation domain (Ogata et al., 2014), it is not predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay, as the final 44 amino acids are replaced by 171 incorrect amino acids. Additionally, no downstream frameshift variants in the TBX1 gene have been reported in the Human Gene Mutation Database to our knowledge. The variant was not observed in approximately 4,900 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 c.1333_1354dup22 variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
