Description
p.Thr549Lys (ACA>AAA): c.1646 C>A in exon 10 of the SOS1 gene (NM_005633.3). The T549K missense change in the SOS1 gene has been reported as a possibly pathogenic variant (Lepri et al., 2011). The T549K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is well conserved across species and is within the helical linker domain, which connects the pleckstrin homology (PH) domain and Ras exchanger motif (REM) (Lepri et al., 2011). Missense mutations in nearby residues (S548R, L550P, R552G, R552K, R552M, R552S, R552T, R552W) within the same domain have been reported in association with Noonan syndrome, supporting the functional importance of this region of the protein. Furthermore, the T549K 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. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in NOONAN panel(s).
| # | 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 |
