Description
The T602I variant in the BTK gene has been reported previously in a male with X-linked agammaglobulinemia (Chun et al., 2008). The T602I variant was not observed in approximately 6,500 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 T602I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Missense variants in nearby residues (P597T, Y598D, Y598S, Y598C, E605G, T606P, A607D) have been reported in the Human Gene Mutation Database in association with agammaglobulinemia (Stenson et al., 2014), supporting the functional importance of this region of the protein. The T602I 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 |
