Description
The S502T variant has been published as an assumed de novo pathogenic variant in a patient diagnosed with Noonan syndrome (Niihori et al., 2005). Another patient who harbored this variant developed leukocytosis and neuroblastoma at 3 months and 6 months of age respectively (Kondoh et al., 2003). In vitro functional studies demonstrated that the presence of the S502T variant resulted in a significant increase in phosphatase activity over wild-type (Niihori et al., 2005). The S502T 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 S502T variant 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 in this residue (S502A, S502L) have been reported in the Human Gene Mutation Database in association with Noonan syndrome (Stenson et al., 2014). Therefore, this variant is pathogenic.
| # | 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 |
