Table 1 A summary of 20 patients identified with pathogenic or likely pathogenic mutations from our cohort using the multigene panel sequencing approach. *Clinical significance was labelled according to the ClinVar database from NCBI (https://www.ncbi.nlm.nih.gov/clinvar/). #Variant class was determined according to the HGMD (Human Gene Mutation Database http://www.hgmd.cf.ac.uk/docs/new_help.html). ^Variant classification was determined according to the NSEuroNet (European Network on Noonan Syndrome and Related Disorders; https://nseuronet.com/php/about.php).
From: Integrating Functional Analysis in the Next-Generation Sequencing Diagnostic Pipeline of RASopathies
Patient number | Gene | Mutation | ClinVar* | HGMD# | NSEuroNet^ | Publication with functional analysis |
|---|---|---|---|---|---|---|
5132 | SOS1 | c.512 T > C:p.(V171A) | likely pathogenic | — | — |  |
15547 | SOS1 | c.1297 G > A:p.(E433K) | pathogenic | disease-causing mutation | Mutation (count = 19) |  |
14626 | SOS1 | c.1644T > G:p.(S548R) | pathogenic | disease-causing mutation | Mutation (count = 1) | Smith et al. (2013) |
5608 | SOS1 | c.1644T > A:p.(S548R) | pathogenic | — | — |  |
6381 | SOS1 | c.1644T > A:p.(S548R) | pathogenic | — | — |  |
9233 | SOS1 | c.1654A > G:p.(R552G) | pathogenic | disease-causing mutation | Mutation (count = 52) |  |
4748 | RAF1 | c.770 C > T:p.(S257L) | likely pathogenic | disease-causing mutation | Mutation (count = 73) |  |
3347 | RAF1 | c.770 C > T:p.(S257L) | likely pathogenic | disease-causing mutation | Mutation (count = 73) |  |
15289 | KRAS | c.13 A > G:p.(K5E) | likely pathogenic | disease-causing mutation | Mutation (count = 3) |  |
4862 | KRAS | c.178 G > A:p.(G60S) | pathogenic | disease-causing mutation | Mutation (count = 1) |  |
15247 | KRAS | c.458 A > T:p.(D153V) | pathogenic | disease-causing mutation | Mutation (count = 13) |  |
6575 | MAP2K1 | c.199 G > A:p.(D67N) | likely pathogenic | — | Mutation (count = 6) |  |
14993 | MAP2K1 | c.371 C > T:p.(P124L) | pathogenic | disease-causing mutation | Mutation (count = 1) | Emery et al. (2009) |
4012 | MAP2K1 | c.389 A > G:p.(Y130C) | pathogenic | disease-causing mutation | Mutation (count = 35) | Cheng et al. (2012) |
14321 | RIT1 | c.170 C > G:p.(A57G) | pathogenic | disease-causing mutation | Mutation (count = 23) | Chen et al. (2014) |
13590 | RIT1 | c.229 G > A:p.(A77T) | likely pathogenic | disease-causing mutation | Mutation (count = 6) |  |
5153 | BRAF | c.1785T > G:p.(F595L) | likely pathogenic | disease-causing mutation | Mutation (count = 5) | Cheng et al. (2012) |
13393 | BRAF | c.1914T > G:p.(D638E) | pathogenic | disease-causing mutation | Mutation (count = 5) | Cheng et al. (2012) |
4749 | SHOC2 | c.4 A > G:p.(S2G) | likely pathogenic | disease-causing mutation | Mutation (count = 169) |  |
5698 | SHOC2 | c.4 A > G:p.(S2G) | likely pathogenic | disease-causing mutation | Mutation (count = 169) |  |
