Table 2 Molecular profiles of nine neonates with RASopathies
Patient number | LOVD Individual ID | Gene | Nucleotide change | Amino acid change | Molecular diagnosis | Inheritance pattern | Zygosity | Variant type | In silico prediction (SIFT/PolyPhen) | ACMG classification | Novel/ published (PMID) | De novo/ inherited | Age of confirmed diagnosis (d) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Patient 1 | 00410414 | PTPN11 (NM_002834.3) | c.1517A > C | p.Gln506Pro | Noonan syndrome 1 (MIM:163,950) | AD | Het | missense | – | Pathogenic (PS2, PM2, PP3, PP4) | Published (14961557) | De novo | 61 |
Patient 2 | 00410466 | PTPN11 (NM_002834.3) | c.182A > G | p.Asp61Gly | Noonan syndrome 1 (MIM:163,950) | AD | Het | missense | – | Pathogenic (PS2, PM2, PP3, PP4) | Published (11704759) | De novo | 49 |
Patient 3 | 00410416 | RAF1 (NM_002880.3) | c.770C > T | p.Ser257Leu | Noonan syndrome 5 (MIM:611,553) | AD | Het | missense | – | Pathogenic (PS2, PM2, PP3, PP4) | Published (17603482) | De novo | 84 |
Patient 4 | 00410417 | RAF1 (NM_002880.3) | c.770C > T | p.Ser257Leu | Noonan syndrome 5 (MIM:611,553) | AD | Het | missense | – | Pathogenic (PS2, PM2, PP3, PP4) | Published (17603482) | De novo | 78 |
Patient 5 | 00410430 | BRAF (NM_004333.5) | c.1405G > A | p.Gly469Arg | Noonan syndrome 7 (MIM:613,706) | AD | Het | missense | – | Likely pathogenic (PS2, PM2, PP1,PP3, PP4) | Published (25157968) | De novo | 58 |
Patient 6 | 00410431 | SHOC2 (NM_007373) | c.4A > G | p.Ser2Gly | Noonan syndrome -like with loose anagen hair 1 (MIM:607,721) | AD | Het | missense | – | Pathogenic (PS2, PM2, PP3, PP4) | Published (19684605) | De novo | 50 |
Patient 7 | 00410432 | RASA1 (NM_002890.2) | c.2828 T > C | p.Leu943Pro | Capillary malformation- arteriovenous malformation 1 (MIM:608,354) | AD | Het | missense | Deleterious/ Probably damaging | Likely pathogenic (PS2, PM2, PM5, PP1, PP3, PP4) | Novel | De novo | 64 |
Patient 8 | 00410433 | RASA1 (NM_002890.2) | c.2001del | p.Pro668Leufs*10 | Capillary malformation- arteriovenous malformation 1 (MIM:608,354) | AD | Het | frameshift | – | Pathogenic (PVS1, PS2, PM2, PP3, PP4) | Novel | De novo | 79 |
Patient 9 | 00410435 | HRAS (NM_005343) | c.37G > T | p.Gly13Cys | Costello syndome (MIM:218,040) | AD | Het | missense | – | Pathogenic (PS2, PM2, PP3, PP4) | Published (16835863) | De novo | 55 |