PTPN11 (Q06124) variants and mutations
PTPN11 (also known as Q06124) is a human protein-coding gene encoding a tyrosine-protein phosphatase non-receptor type 11 protein. Its SHP2 phosphatase activity promotes RAS-MAPK signaling downstream of many receptor tyrosine kinases and cytokine receptors. Germline dysregulating variants cause Noonan-spectrum disorders, while somatic activating variants drive juvenile myelomonocytic leukemia and other cancers. This analysis covers 1,792 PTPN11 variants and mutations. Of these, 38% have computational variant effect predictions. Disease context includes Noonan syndrome, Noonan syndrome with multiple lentigines, and juvenile myelomonocytic leukemia. Example PTPN11 variants include T2A, T2I, and T2K.
Variant analysis overview
- Gene: PTPN11
- Protein: Q06124
- UniProt accession: Q06124
- Organism: Homo sapiens
- Variants analyzed: 1792
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 1,663 unspecified-consequence records; 29 missense variants; 87 synonymous variants; 2 stop-gained variants; 4 splice-region variants; 1 frameshift variants; 1 in-frame deletions; 4 substitution
- Prediction scores: 687 variants have prediction scores (38% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Noonan syndrome, Noonan syndrome with multiple lentigines, juvenile myelomonocytic leukemia, LEOPARD syndrome 1, metachondromatosis, acute myeloid leukemia, cancer, RASopathy, Noonan syndrome and Noonan-related syndrome, Abnormality of the cardiovascular system, Noonan syndrome 3, male infertility with azoospermia or oligozoospermia due to single gene mutation.
Protein structure and variant hotspots
- Protein features: 3 domains; 3 binding sites; 5 post-translational modification sites.
- Structural context: 1,550 variants have structural context.
- PTM context: 20 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable PTPN11 variants
Examples include T2A, T2I, T2K, T2T, S3L, S3W, S3*, S3S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- T2A (p.Thr2Ala), Ensembl rs2135817439, REVEL 0.05, MetaLR 0.17
- T2I (p.Thr2Ile), rs267606990, ClinGen CA256764, ClinVar RCV000014277, ClinVar RCV000033445, REVEL 0.21, MetaLR 0.23, Pathogenic/Likely pathogenic, LEOPARD syndrome 1; Noonan syndrome 1; Metachondromatosis
- T2K (p.Thr2Lys), gnomAD 12-112419116-C-A, REVEL 0.15, CADD 24.50
- T2T (p.Thr2Thr), rs768238710, gnomAD 12-112419117-A-T, CADD 17.20
- S3L (p.Ser3Leu), Ensembl rs2135817459, REVEL 0.63, MetaLR 0.91
- S3W (p.Ser3Trp), Ensembl rs2135817459
- S3* (p.Ser3Ter), gnomAD 12-112419119-C-A, CADD 48.00
- S3S (p.Ser3Ser), gnomAD 12-112419120-G-T, CADD 18.20
- R4G (p.Arg4Gly), rs886041517, ClinGen CA10603227, ClinVar RCV000353023, ClinVar RCV006462297, REVEL 0.52, MetaLR 0.84, Conflicting interpretations, not provided; RASopathy
- R4Q (p.Arg4Gln), rs2499756229, ClinGen CA386773580, ClinVar RCV003540107, REVEL 0.39, MetaLR 0.74, Likely pathogenic, RASopathy
- R4W (p.Arg4Trp), TOPMed rs886041517, REVEL 0.77, MetaLR 0.91, Likely benign
- R4R (p.Arg4Arg), rs886041517, gnomAD 12-112419121-C-A, CADD 16.50
- R4L (p.Arg4Leu), gnomAD 12-112419122-G-T, REVEL 0.43, CADD 26.10
- R5G (p.Arg5Gly), Ensembl rs587781133, REVEL 0.56, MetaLR 0.79
- R5R (p.Arg5Arg), gnomAD 12-112419124-A-C, CADD 23.70
- R5* (p.Arg5Ter), gnomAD 12-112419124-A-T, CADD 44.00
- R5I (p.Arg5Ile), gnomAD 12-112419125-G-T, REVEL 0.82, CADD 47.00
- W6C (p.Trp6Cys), rs79203122, ClinGen CA243707497, cosmic curated COSV10069, ClinVar RCV003655507, REVEL 0.92, MetaLR 0.96, Uncertain significance, Cardiovascular phenotype; RASopathy
- W6L (p.Trp6Leu), gnomAD 12-112446278-G-T, REVEL 0.90, MetaLR 0.96
- H8Y (p.His8Tyr), Ensembl rs2135856276
- P9A (p.Pro9Ala), 1000Genomes rs566068139, ExAC rs566068139, gnomAD rs566068139, REVEL 0.54, MetaLR 0.80
- P9Q (p.Pro9Gln), 1000Genomes rs536503257, ExAC rs536503257, gnomAD rs536503257, REVEL 0.68, MetaLR 0.84
- P9R (p.Pro9Arg), 1000Genomes rs536503257, ExAC rs536503257, gnomAD rs536503257, REVEL 0.59, MetaLR 0.78
- P9S (p.Pro9Ser), 1000Genomes rs566068139, ExAC rs566068139, gnomAD rs566068139, REVEL 0.66, MetaLR 0.82
- N10D (p.Asn10Asp), rs368633510, ClinGen CA6798505, ClinVar RCV001040499, ClinVar RCV002282433, REVEL 0.37, AlphaMissense 0.35, Uncertain significance, Cardiovascular phenotype; RASopathy; not provided
- N10H (p.Asn10His), rs368633510, ClinGen CA386776144, ClinVar RCV002247769, ESP rs368633510, AlphaMissense 0.35, MetaLR 0.56, Uncertain significance, Metachondromatosis
- N10I (p.Asn10Ile), 1000Genomes rs200613531, ExAC rs200613531, TOPMed rs200613531, gnomAD rs200613531, Uncertain significance
- N10S (p.Asn10Ser), rs200613531, ClinGen CA6798506, ClinVar RCV002979245, ClinVar RCV004763497, REVEL 0.40, AlphaMissense 0.17, Uncertain significance, not provided; RASopathy
- N10T (p.Asn10Thr), rs200613531, ClinGen CA386776146, ClinVar RCV003539596, ClinVar RCV005220744, AlphaMissense 0.17, MetaLR 0.46, Uncertain significance, not provided; RASopathy
- N10Y (p.Asn10Tyr), rs368633510, ClinGen CA386776145, ClinVar RCV003339290, ClinVar RCV004784143, AlphaMissense 0.35, MetaLR 0.56, Uncertain significance, RASopathy; Cardiovascular phenotype; not provided
- I11T (p.Ile11Thr), rs1181579972, ClinGen CA386776154, ClinVar RCV003539587, gnomAD rs1181579972, REVEL 0.88, MetaLR 0.83, Uncertain significance, RASopathy
- I11V (p.Ile11Val), gnomAD rs1472357430, REVEL 0.42, MetaLR 0.68
- T12A (p.Thr12Ala), rs1386827892, ClinGen CA386776158, ClinVar RCV001893199, gnomAD rs1386827892, REVEL 0.51, MetaLR 0.85, Uncertain significance, Cardiovascular phenotype; RASopathy
- T12S (p.Thr12Ser), gnomAD 12-112446295-A-T, REVEL 0.40, MetaLR 0.55
- T12T (p.Thr12Thr), rs760086740, gnomAD 12-112446297-T-C, CADD 10.90
- G13D (p.Gly13Asp), NCI-TCGA Cosmic COSV6101, cosmic curated COSV61011, Variant assessed as somatic; moderate impact.
- G13S (p.Gly13Ser), Ensembl rs2135856346
- G13G (p.Gly13Gly), gnomAD 12-112446300-T-C, CADD 8.00
- V14M (p.Val14Met), cosmic curated COSV10465, Ensembl rs2135856353, Uncertain significance, RASopathy; not provided
- E15K (p.Glu15Lys), gnomAD 12-112446304-G-A, REVEL 0.69, MetaLR 0.70
- E15E (p.Glu15Glu), gnomAD 12-112446306-G-A, CADD 11.10
- A16G (p.Ala16Gly), Ensembl rs2135856364
- A16T (p.Ala16Thr), cosmic curated COSV61012, Ensembl rs2135856357
- A16V (p.Ala16Val), cosmic curated COSV61006, Ensembl rs2135856364
- A16A (p.Ala16Ala), rs372736227, gnomAD 12-112446309-A-G, CADD 9.73
- N18D (p.Asn18Asp), ExAC rs776089364, gnomAD rs776089364, REVEL 0.31, MetaLR 0.35, Uncertain significance, Cardiovascular phenotype
- N18S (p.Asn18Ser), rs587778635, ClinGen CA161776, ClinVar RCV000121911, ClinVar RCV000261129, REVEL 0.30, MetaLR 0.35, Benign, RASopathy
- N18K (p.Asn18Lys), gnomAD 12-112446315-C-G, REVEL 0.33, MetaLR 0.21
- L19R (p.Leu19Arg), Ensembl rs397507500
- L19V (p.Leu19Val), rs2037993841, ClinGen CA386776204, ClinVar RCV003655713, gnomAD rs2037993841, REVEL 0.60, MetaLR 0.85, Uncertain significance, RASopathy
- L19L (p.Leu19Leu), rs764238610, gnomAD 12-112446318-A-G, CADD 8.54
- L20V (p.Leu20Val), ExAC rs753951666, gnomAD rs753951666, REVEL 0.85, MetaLR 0.98
- L20L (p.Leu20Leu), gnomAD 12-112446319-C-T, CADD 12.40
- L21W (p.Leu21Trp), gnomAD 12-112446323-T-G, REVEL 0.79, MetaLR 0.85
- L21L (p.Leu21Leu), gnomAD 12-112446324-G-A, CADD 11.80
- T22A (p.Thr22Ala), rs757537175, ClinGen CA6798511, ClinVar RCV001261096, ClinVar RCV003539390, REVEL 0.37, MetaLR 0.35, Uncertain significance, LEOPARD syndrome 1; Noonan syndrome 1; Juvenile myelomonocytic leukemia
- T22P (p.Thr22Pro), gnomAD 12-112446325-A-C, REVEL 0.39, MetaLR 0.47
- T22T (p.Thr22Thr), rs397516808, gnomAD 12-112446327-A-G, CADD 9.45
- R23K (p.Arg23Lys), NCI-TCGA Cosmic COSV6100, cosmic curated COSV61005, Variant assessed as somatic; moderate impact.
- R23S (p.Arg23Ser), gnomAD 12-112446330-A-C, REVEL 0.60, MetaLR 0.48
- G24* (p.Gly24Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- V25I (p.Val25Ile), cosmic curated COSV61012, TOPMed rs2037994211
- D26N (p.Asp26Asn), ExAC rs750261927, gnomAD rs750261927, REVEL 0.39, MetaLR 0.65, Uncertain significance, RASopathy
- D26V (p.Asp26Val), gnomAD rs1247363600, REVEL 0.77, MetaLR 0.65
- D26Y (p.Asp26Tyr), ExAC rs750261927, gnomAD rs750261927, REVEL 0.74, MetaLR 0.86
- D26E (p.Asp26Glu), gnomAD 12-112446339-T-G, REVEL 0.32, MetaLR 0.52
- D26D (p.Asp26Asp), gnomAD 12-112446339-T-C, CADD 12.30
- G27D (p.Gly27Asp), rs2135856448, ClinGen CA386776253, ClinVar RCV001508340, Ensembl rs2135856448, AlphaMissense 1.00, MetaLR 0.99, Uncertain significance, not provided
- G27S (p.Gly27Ser), cosmic curated COSV10069
- S28N (p.Ser28Asn), Ensembl rs2135856451, REVEL 0.74, MetaLR 0.84
- S28R (p.Ser28Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S28G (p.Ser28Gly), gnomAD 12-112446343-A-G, REVEL 0.84, MetaLR 0.81
- L30* (p.Leu30Ter), Ensembl rs2135856455
- L30F (p.Leu30Phe), gnomAD 12-112446351-G-T, REVEL 0.91, MetaLR 0.99
- A31E (p.Ala31Glu), Ensembl rs2037994433, Likely pathogenic
- A31G (p.Ala31Gly), rs2037994433, ClinGen CA386776282, ClinVar RCV001253203, Ensembl rs2037994433, AlphaMissense 1.00, MetaLR 0.84, Likely pathogenic, LEOPARD syndrome 1
- A31S (p.Ala31Ser), rs2540410654, ClinGen CA386776280, ClinVar RCV002284931, Uncertain significance, not provided
- A31V (p.Ala31Val), Ensembl rs2037994433, Likely pathogenic
- R32M (p.Arg32Met), Ensembl rs2135856466
- R32R (p.Arg32Arg), gnomAD 12-112446357-G-A, CADD 10.50
- P33L (p.Pro33Leu), NCI-TCGA Cosmic COSV6100, cosmic curated COSV61009, Variant assessed as somatic; moderate impact.
- P33S (p.Pro33Ser), cosmic curated COSV61006
- P33P (p.Pro33Pro), rs2135856472, gnomAD 12-112446360-T-C, CADD 13.90
- S34N (p.Ser34Asn), Ensembl rs906966059, REVEL 0.81, MetaLR 0.95
- K35E (p.Lys35Glu), rs934388335, ClinGen CA243707499, ClinVar RCV001204608, gnomAD rs934388335, REVEL 0.37, MetaLR 0.33, Uncertain significance, RASopathy; Cardiovascular phenotype
- K35I (p.Lys35Ile), rs2037994651, ClinGen CA386776308, ClinVar RCV003540187, gnomAD rs2037994651, REVEL 0.60, MetaLR 0.57, Uncertain significance, RASopathy
- K35Q (p.Lys35Gln), rs934388335, ClinGen CA386776304, ClinVar RCV000681118, ClinVar RCV004026167, REVEL 0.25, MetaLR 0.38, Uncertain significance, Cardiovascular phenotype; not provided
- S36C (p.Ser36Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S36G (p.Ser36Gly), Ensembl rs2135856496
- S36S (p.Ser36Ser), rs1312842293, gnomAD 12-112446369-T-C, CADD 10.40
- N37K (p.Asn37Lys), gnomAD rs1337565783, REVEL 0.35, MetaLR 0.37, Uncertain significance, RASopathy
- N37T (p.Asn37Thr), cosmic curated COSV61010
- P38H (p.Pro38His), cosmic curated COSV61013
- P38S (p.Pro38Ser), cosmic curated COSV10969
- P38P (p.Pro38Pro), rs758209360, gnomAD 12-112446375-T-G, CADD 9.63
- G39R (p.Gly39Arg), rs886041585, TOPMed rs886041585, gnomAD rs886041585, ClinGen CA10603228, REVEL 0.92, MetaLR 0.94, Uncertain significance, not provided; RASopathy
- G39G (p.Gly39Gly), rs779813529, gnomAD 12-112446378-A-C, CADD 12.90
- D40G (p.Asp40Gly), rs397516795, ClinGen CA134635, NCI-TCGA Cosmic COSV1006, cosmic curated COSV10069, AlphaMissense 0.99, MetaLR 0.64, Uncertain significance, not specified
- F41L (p.Phe41Leu), Ensembl rs2037995014
- F41S (p.Phe41Ser), Ensembl rs2135856548
- T42A (p.Thr42Ala), rs397507501, ClinGen CA235307, NCI-TCGA Cosmic COSV6100, cosmic curated COSV61008, AlphaMissense 0.99, MetaLR 0.52, Pathogenic, PTPN11-related disorder; Cardiovascular phenotype; Noonan syndrome and Noonan-re
- T42T (p.Thr42Thr), rs2037995126, gnomAD 12-112446387-A-G, CADD 7.86
- L43F (p.Leu43Phe), rs1566164987, ClinGen CA386776360, ClinVar RCV000680807, ClinVar RCV000805888, AlphaMissense 0.96, MetaLR 0.96, Conflicting interpretations, not specified; Metachondromatosis; LEOPARD syndrome 1
- L43I (p.Leu43Ile), Ensembl rs1566164987, Uncertain significance
- L43V (p.Leu43Val), rs1566164987, ClinGen CA386776359, ClinVar RCV001829267, ClinVar RCV002503336, REVEL 0.82, AlphaMissense 0.96, Uncertain significance, Cardiovascular phenotype; Metachondromatosis; Juvenile myelomonocytic leukemia
- L43L (p.Leu43Leu), gnomAD 12-112446390-T-G, CADD 8.55
- S44C (p.Ser44Cys), Ensembl rs2135856577
- S44F (p.Ser44Phe), cosmic curated COSV10969, cosmic curated COSV61010
- S44S (p.Ser44Ser), rs397507502, gnomAD 12-112446393-C-T, CADD 3.74
- V45F (p.Val45Phe), NCI-TCGA Cosmic COSV6100, NCI-TCGA Cosmic COSV9908, Variant assessed as somatic; moderate impact.
- V45G (p.Val45Gly), cosmic curated COSV10650
- V45I (p.Val45Ile), rs2037995352, ClinGen CA386776370, NCI-TCGA Cosmic COSV6100, cosmic curated COSV61009, REVEL 0.56, MetaLR 0.75, Uncertain significance, RASopathy; not provided
- V45L (p.Val45Leu), NCI-TCGA Cosmic COSV6100, NCI-TCGA Cosmic COSV9908, cosmic curated COSV99080, Ensembl rs2037995352, REVEL 0.74, MetaLR 0.80, Uncertain significance
- R46G (p.Arg46Gly), cosmic curated COSV61005
- R47* (p.Arg47Ter), Ensembl rs2135861847
- R47G (p.Arg47Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R47K (p.Arg47Lys), Ensembl rs2135861852
- R47T (p.Arg47Thr), Ensembl rs2135861852
- N48H (p.Asn48His), TOPMed rs2038060556
- N48S (p.Asn48Ser), ExAC rs765495843, gnomAD rs765495843, REVEL 0.46, MetaLR 0.74
- G49* (p.Gly49Ter), Ensembl rs2135861867, Uncertain significance
- G49A (p.Gly49Ala), Ensembl rs2135861872
- G49E (p.Gly49Glu), Ensembl rs2135861872
- G49R (p.Gly49Arg), rs2135861867, ClinGen CA386777384, ClinVar RCV001586630, ClinVar RCV005601788, REVEL 0.81, MetaLR 0.86, Uncertain significance, not provided; Ewing sarcoma
- G49V (p.Gly49Val), Ensembl rs2135861872
- G49G (p.Gly49Gly), rs2135861881, gnomAD 12-112450327-A-G, CADD 12.50, SIFT 0.09
- A50G (p.Ala50Gly), Ensembl rs2135861893
- A50P (p.Ala50Pro), ExAC rs587778636, gnomAD rs587778636, REVEL 0.52, MetaLR 0.59, Uncertain significance
- A50T (p.Ala50Thr), rs587778636, ClinGen CA161779, NCI-TCGA Cosmic COSV6100, cosmic curated COSV61007, REVEL 0.31, MetaLR 0.48, Uncertain significance, RASopathy
- A50V (p.Ala50Val), Ensembl rs2135861893
- V51A (p.Val51Ala), Ensembl rs2135861904
- V51I (p.Val51Ile), Ensembl rs2135861898, REVEL 0.55, MetaLR 0.77
- V51L (p.Val51Leu), Ensembl rs2135861898
- V51V (p.Val51Val), gnomAD 12-112450333-C-A, CADD 9.44, SIFT 0.10
- T52A (p.Thr52Ala), NCI-TCGA Cosmic COSV6100, cosmic curated COSV61007, Variant assessed as somatic; moderate impact.
- T52I (p.Thr52Ile), rs397507503, ClinGen CA261555, NCI-TCGA Cosmic COSV6100, NCI-TCGA Cosmic COSV6101, REVEL 0.91, MetaLR 0.78, Pathogenic, RASopathy
- T52N (p.Thr52Asn), Ensembl rs397507503, Uncertain significance, RASopathy
- T52S (p.Thr52Ser), NCI-TCGA Cosmic COSV6100, cosmic curated COSV61006, NCI-TCGA Cosmic COSV6101, Ensembl rs397507503, Likely pathogenic
- T52T (p.Thr52Thr), rs147388185, gnomAD 12-112450336-C-T, CADD 9.81, SIFT 0.00
- H53D (p.His53Asp), Ensembl rs2135861929
- H53L (p.His53Leu), Ensembl rs2135861937
- H53N (p.His53Asn), Ensembl rs2135861929
- H53Q (p.His53Gln), ExAC rs766205831, gnomAD rs766205831
- H53Y (p.His53Tyr), Ensembl rs2135861929, REVEL 0.95, MetaLR 0.98
- H53H (p.His53His), rs766205831, gnomAD 12-112450339-C-T, CADD 11.20, SIFT 0.04
- I54F (p.Ile54Phe), Ensembl rs2135861950
- I54M (p.Ile54Met), cosmic curated COSV10606, TOPMed rs1207829516, gnomAD rs1207829516, Likely benign
- I54N (p.Ile54Asn), Ensembl rs2135861953
- I54T (p.Ile54Thr), NCI-TCGA Cosmic COSV6100, cosmic curated COSV61007, Variant assessed as somatic; moderate impact.
- I54I (p.Ile54Ile), rs1207829516, gnomAD 12-112450342-C-T, CADD 12.70
- K55E (p.Lys55Glu), Ensembl rs2135861965
- K55M (p.Lys55Met), TOPMed rs1261667540, Uncertain significance
- K55N (p.Lys55Asn), NCI-TCGA Cosmic COSV6100, cosmic curated COSV61005, Ensembl rs2135861980, Variant assessed as somatic; moderate impact.
- K55R (p.Lys55Arg), rs1261667540, ClinGen CA386777492, ClinVar RCV001912687, TOPMed rs1261667540, REVEL 0.55, MetaLR 0.48, Uncertain significance, RASopathy
- K55T (p.Lys55Thr), cosmic curated COSV10969
- K55K (p.Lys55Lys), gnomAD 12-112450345-G-A, CADD 10.90, SIFT 0.15
- I56F (p.Ile56Phe), cosmic curated COSV10069, TOPMed rs397507504, gnomAD rs397507504, Pathogenic
- I56N (p.Ile56Asn), TOPMed rs1052382672, Likely pathogenic
- I56S (p.Ile56Ser), TOPMed rs1052382672, Likely pathogenic
- I56T (p.Ile56Thr), rs1052382672, ClinGen CA243707917, ClinVar RCV000531774, ClinVar RCV000788007, AlphaMissense 1.00, MetaLR 0.98, Likely pathogenic, Noonan syndrome and Noonan-related syndrome
- I56V (p.Ile56Val), rs397507504, ClinGen CA180973, ClinVar RCV000154561, ClinVar RCV000518841, REVEL 0.77, MetaLR 0.94, Pathogenic, Noonan syndrome and Noonan-related syndrome
- Q57* (p.Gln57Ter), Ensembl rs2135861999
- Q57E (p.Gln57Glu), Ensembl rs2135861999
- Q57H (p.Gln57His), rs2135862010, Ensembl rs2135862010, ClinGen CA386777534, ClinVar RCV001261097, AlphaMissense 1.00, MetaLR 0.60, Likely pathogenic, Noonan syndrome
- Q57K (p.Gln57Lys), Ensembl rs2135861999
- Q57L (p.Gln57Leu), Ensembl rs2135862007
- Q57R (p.Gln57Arg), Ensembl rs2135862007
- Q57Q (p.Gln57Gln), rs2135862010, gnomAD 12-112450351-G-A, AlphaMissense 1.00, MetaLR 0.60
- N58D (p.Asn58Asp), rs397507505, ClinGen CA261558, cosmic curated COSV10818, ClinVar RCV000033455, AlphaMissense 0.93, MetaLR 0.75, Pathogenic, PTPN11-related disorder; Noonan syndrome and Noonan-related syndrome; Male infer
- N58H (p.Asn58His), rs397507505, ClinGen CA235310, cosmic curated COSV10969, ClinVar RCV000037626, AlphaMissense 0.93, MetaLR 0.75, Pathogenic, not provided; RASopathy; Noonan syndrome
- N58I (p.Asn58Ile), ExAC rs751437780, TOPMed rs751437780, gnomAD rs751437780, Likely pathogenic, in NS1
- N58K (p.Asn58Lys), rs397507506, ClinGen CA235313, cosmic curated COSV61010, ClinVar RCV000037629, AlphaMissense 1.00, MetaLR 0.66, Pathogenic/Likely pathogenic, PTPN11-related disorder; LEOPARD syndrome 1; Noonan syndrome 1
- N58S (p.Asn58Ser), rs751437780, ClinGen CA6798530, cosmic curated COSV61005, ClinVar RCV000413828, REVEL 0.61, MetaLR 0.56, Conflicting interpretations, Cardiovascular phenotype; Noonan syndrome 1; Metachondromatosis
- N58Y (p.Asn58Tyr), rs397507505, ClinGen CA297070, NCI-TCGA Cosmic COSV6100, cosmic curated COSV61007, AlphaMissense 0.93, MetaLR 0.75, Pathogenic/Likely pathogenic, not provided; RASopathy
- T59A (p.Thr59Ala), rs886043790, ClinGen CA10605950, ClinVar RCV000390743, ClinVar RCV001349385, REVEL 0.71, MetaLR 0.60, Conflicting interpretations, Autosomal dominant PTPN11-related disorders; PTPN11-related disorder; Cardiovasc
- T59I (p.Thr59Ile), Ensembl rs2135862036
- T59N (p.Thr59Asn), Ensembl rs2135862036
- T59S (p.Thr59Ser), TOPMed rs886043790, gnomAD rs886043790, Pathogenic, in NS1
- G60A (p.Gly60Ala), rs397507509, ClinGen CA261562, NCI-TCGA Cosmic COSV1006, NCI-TCGA Cosmic COSV6100, REVEL 0.91, AlphaMissense 1.00, Pathogenic, PTPN11-related disorder; Noonan syndrome and Noonan-related syndrome; Cardiovasc
- G60C (p.Gly60Cys), rs397507507, ClinGen CA215448, ClinVar RCV000034327, ClinVar RCV002408501, AlphaMissense 1.00, MetaLR 0.94, Pathogenic/Likely pathogenic, Congenital anomaly of kidney and urinary tract; Congenital heart disease; Cardio
Public PTPN11 analysis runs
- PTPN11 analysis run — PTPN11 (1,792 variants) — completed 2026-08-18