Description
The A72V missense variant in the PTPN11 gene has been reported previously in association with leukemogenesis in Noonan syndrome (Tartaglia et al., 2006; Bocchinfuso et al., 2007). It 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. A72V is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants at the same codon (A72S, A72P, A72G) and in nearby residues (Y62N/C, Y63C, E69Q/V, F71I, T73I, E76I/G/A/D/, Q79P/R) have been reported in the Human Gene Mutation Database in association with Noonan syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. In addition, functional studies of the A72V variant have shown that it results in a conformational shift impairing interactions between the N-SH2 domain and catalytic site while displacing the N-SH2 loop of the protein (Bocchoinfuso et al., 2007).
| # | 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 |
