Total 57 pathogenic variants reported for Costello syndrome 
Variant Name Variant Type Variant Genomic Location Clinical Significance Phenotype Condition Review Status ClinGen Allele dbSNP ID Variation/condition record
NM_005343.4(HRAS):c.35G>T (p.Gly12Val) SNV
Germline/somatic		 Chr11:534288 Pathogenic Malignant tumor of urinary bladder
Costello syndrome
Myopathy, congenital, with excess of muscle spindles
Epidermal nevus
Condition: not provided
HRAS-related disorder
Cardiovascular phenotype		 Criteria Provided
Multiple Submitters
No Conflicts
 CA122545 rs_104894230

8 SubmittersRCV000013431RCV000013432RCV000013433RCV000032850RCV000157912RCV003415692RCV004018622
NM_005343.4(HRAS):c.34G>A (p.Gly12Ser) SNV
Germline/somatic		 Chr11:534289 Pathogenic Costello syndrome
Myopathy, congenital, with excess of muscle spindles
Nevus sebaceous
EPIDERMAL NEVUS WITH UROTHELIAL CANCER, SOMATIC
Condition: not provided
RASopathy
Wooly hair nevus
Lip and oral cavity carcinoma
Rhabdomyosarcoma
Noonan syndrome and Noonan-related syndrome
Cardiovascular phenotype
Noonan syndrome 1
Epidermal nevus
See cases
HRAS-related disorder
Embryonal rhabdomyosarcoma		 Reviewed By Expert Panel
 CA122549 rs_104894229

41 SubmittersRCV000013435RCV000013436RCV000029209RCV000022796RCV000081295RCV000149828RCV000487471RCV001255689RCV001257537RCV001813185RCV002453256RCV003450635RCV003450636RCV003156059RCV003398496RCV006253536
NM_005343.4(HRAS):c.35G>C (p.Gly12Ala) SNV
Germline		 Chr11:534288 Pathogenic Costello syndrome
Condition: not provided
Inborn genetic diseases
6 conditions
Rhabdomyosarcoma
Noonan syndrome and Noonan-related syndrome		 Criteria Provided
Multiple Submitters
No Conflicts
 CA256486 rs_104894230

10 SubmittersRCV000013437RCV000207503RCV000623953RCV000762848RCV001257536RCV001813186
NM_005343.4(HRAS):c.38G>A (p.Gly13Asp) SNV
Germline/somatic		 Chr11:534285 Pathogenic Costello syndrome
Condition: not provided
RASopathy
Non-immune hydrops fetalis
Noonan syndrome and Noonan-related syndrome
6 conditions
HRAS-related disorder
Malignant tumor of urinary bladder
Melanoma
Embryonal rhabdomyosarcoma		 Criteria Provided
Multiple Submitters
No Conflicts
 CA256488 rs_104894226

18 SubmittersRCV000013438RCV000157913RCV000781469RCV001376018RCV001813187RCV002476960RCV003390677RCV005887484RCV005887485RCV006253537
NM_005343.4(HRAS):c.350A>G (p.Lys117Arg) SNV
Germline		 Chr11:533553 Pathogenic Costello syndrome
Condition: not provided
RASopathy		 Reviewed By Expert Panel
 CA256490 rs_104894227

5 SubmittersRCV000013439RCV000353386RCV005252033
NM_005343.4(HRAS):c.37G>T (p.Gly13Cys) SNV
Germline/somatic		 Chr11:534286 Pathogenic Costello syndrome
RASopathy
Condition: not provided
Noonan syndrome
6 conditions
Noonan syndrome and Noonan-related syndrome
HRAS-related disorder
Linear nevus sebaceous syndrome
Rhabdomyosarcoma		 Reviewed By Expert Panel
 CA295247 rs_104894228

20 SubmittersRCV000013440RCV000149831RCV000207504RCV000678903RCV000762847RCV001813188RCV003421918RCV004767004RCV006253538
NM_005343.4(HRAS):c.436G>A (p.Ala146Thr) SNV
Germline		 Chr11:533467 Pathogenic Costello syndrome No Assertion Criteria Provided
 CA256492 rs_104894231

1 SubmittersRCV000013441
NM_005343.4(HRAS):c.187G>A (p.Glu63Lys) SNV
Germline		 Chr11:533869 Pathogenic Myopathy, congenital, with excess of muscle spindles
Condition: not provided
Costello syndrome		 Criteria Provided
Multiple Submitters
No Conflicts
 CA122551 rs_121917756

3 SubmittersRCV000013442RCV000485616RCV002272015
NM_005343.4(HRAS):c.64C>A (p.Gln22Lys) SNV
Germline		 Chr11:534259 Likely pathogenic Myopathy, congenital, with excess of muscle spindles
Costello syndrome
Condition: not provided
HRAS-related disorder		 Criteria Provided
Multiple Submitters
No Conflicts
 CA122553 rs_121917757

6 SubmittersRCV000013443RCV000143898RCV000157915RCV005867747
NM_005343.4(HRAS):c.173C>T (p.Thr58Ile) SNV
Germline		 Chr11:533883 Pathogenic Costello syndrome
Condition: not provided
HRAS-related disorder
RASopathy		 Reviewed By Expert Panel
 CA341206 rs_121917758

9 SubmittersRCV000013444RCV003221783RCV004724738RCV005252034
NM_005343.4(HRAS):c.437C>T (p.Ala146Val) SNV
Germline		 Chr11:533466 Likely pathogenic Costello syndrome Criteria Provided
Multiple Submitters
No Conflicts
 CA256494 rs_121917759

3 SubmittersRCV000013445
NM_005343.4(HRAS):c.34G>T (p.Gly12Cys) SNV
Germline/somatic		 Chr11:534289 Pathogenic Costello syndrome
Nevus sebaceous
Epidermal nevus
RASopathy
Condition: not provided
6 conditions
Embryonal rhabdomyosarcoma		 Criteria Provided
Multiple Submitters
No Conflicts
 CA129948 rs_104894229

15 SubmittersRCV000013447RCV000029211RCV000032851RCV000149829RCV000212495RCV000762849RCV006253539
NM_005343.4(HRAS):c.37G>C (p.Gly13Arg) SNV
Germline/somatic		 Chr11:534286 Pathogenic/Likely pathogenic Nevus sebaceous
Linear nevus sebaceous syndrome
Epidermal nevus
SPITZ NEVUS, SOMATIC
NEVUS SPILUS, SOMATIC
Lip and oral cavity carcinoma
Non-immune hydrops fetalis
Costello syndrome
cutaneous-skeletal hypophosphatemia syndrome
Noonan syndrome and Noonan-related syndrome
HRAS-related disorder
Ectomesenchymoma
Alveolar rhabdomyosarcoma
Breast phyllodes tumor
Embryonal rhabdomyosarcoma		 Criteria Provided
Multiple Submitters
No Conflicts
 CA129950 rs_104894228

11 SubmittersRCV000029212RCV000029213RCV000032852RCV000173006RCV000173005RCV001255682RCV001376004RCV001781319RCV001849283RCV001813211RCV004739310RCV006253696RCV006253693RCV006253695RCV006253694
NM_005343.4(HRAS):c.175G>A (p.Ala59Thr) SNV
Germline		 Chr11:533881 Likely pathogenic Non-small cell lung carcinoma
Costello syndrome
RASopathy		 Reviewed By Expert Panel
 CA176353 rs_727503093

5 SubmittersRCV000150834RCV000150835RCV004760350
NM_005343.4(HRAS):c.179G>A (p.Gly60Asp) SNV
Germline		 Chr11:533877 Pathogenic Condition: not provided
Costello syndrome		 Criteria Provided
Multiple Submitters
No Conflicts
 CA296057 rs_730880460

3 SubmittersRCV000157917RCV001387769
NM_005343.4(HRAS):c.460G>A (p.Asp154Asn) SNV
Germline		 Chr11:532746 Conflicting classifications of pathogenicity Condition: not provided
Costello syndrome
not specified
Cardiovascular phenotype		 Criteria Provided
Conflicting Classifications
 CA5779226 rs_745497215

5 SubmittersRCV000434487RCV000637302RCV006456635RCV005851505
NM_005343.4(HRAS):c.45C>T (p.Gly15=) SNV
Germline		 Chr11:534278 Conflicting classifications of pathogenicity not specified
Condition: not provided
Costello syndrome
Hereditary cancer-predisposing syndrome
HRAS-related disorder		 Criteria Provided
Conflicting Classifications
 CA183700 rs_727504614

5 SubmittersRCV000155869RCV000585962RCV000818776RCV002257458RCV003952786
NM_005343.4(HRAS):c.418C>T (p.Pro140Ser) SNV
Germline		 Chr11:533485 Conflicting classifications of pathogenicity not specified
Costello syndrome		 Criteria Provided
Conflicting Classifications
 CA180880 rs_144001095

2 SubmittersRCV000154499RCV000700279
NM_005343.4(HRAS):c.38G>T (p.Gly13Val) SNV
Germline/somatic		 Chr11:534285 Pathogenic/Likely pathogenic Condition: not provided
Costello syndrome
Lip and oral cavity carcinoma
KA-like vemurafenib-induced squamous lesions
Linear nevus sebaceous syndrome
Large congenital melanocytic nevus
Rhabdomyosarcoma
Neoplasm		 Criteria Provided
Multiple Submitters
No Conflicts
 CA296055 rs_104894226

12 SubmittersRCV000157914RCV000590121RCV001255688RCV001849323RCV004767097RCV004562310RCV006253847RCV006273570
NM_004333.6(BRAF):c.1661T>C (p.Ile554Thr) SNV
Germline		 Chr7:140776945 Conflicting classifications of pathogenicity RASopathy
Costello syndrome
not specified		 Criteria Provided
Conflicting Classifications
 CA10582465 rs_878854675

3 SubmittersRCV000231445RCV001261046RCV005434739
NM_005343.4(HRAS):c.546G>A (p.Met182Ile) SNV
Germline		 Chr11:532660 Conflicting classifications of pathogenicity Costello syndrome
not specified
6 conditions		 Criteria Provided
Conflicting Classifications
 CA5779209 rs_748639813

4 SubmittersRCV000229010RCV003993902RCV005049496
NM_005343.4(HRAS):c.171T>C (p.Asp57=) SNV
Germline		 Chr11:533885 Conflicting classifications of pathogenicity not specified
Costello syndrome
Hereditary cancer-predisposing syndrome
Condition: not provided		 Criteria Provided
Conflicting Classifications
 CA5779392 rs_776105083

4 SubmittersRCV000246927RCV000871401RCV002258867RCV006263805
NM_005343.4(HRAS):c.34G>C (p.Gly12Arg) SNV
Germline		 Chr11:534289 Likely pathogenic Costello syndrome Criteria Provided
Single Submitter
 CA16602439 rs_104894229

1 SubmittersRCV002230756
NM_005343.4(HRAS):c.37G>A (p.Gly13Ser) SNV
Germline/somatic		 Chr11:534286 Likely pathogenic Vascular Tumors Including Pyogenic Granuloma
Costello syndrome		 Criteria Provided
Single Submitter
 CA16602769 rs_104894228

2 SubmittersRCV000662270RCV002524694
NM_005343.4(HRAS):c.179G>T (p.Gly60Val) SNV
Germline		 Chr11:533877 Pathogenic Condition: not provided
6 conditions
Costello syndrome		 Criteria Provided
Multiple Submitters
No Conflicts
 CA16606948 rs_730880460

3 SubmittersRCV000443979RCV002060067RCV005090865
NM_005343.4(HRAS):c.451-5C>G SNV
Germline		 Chr11:532760 Conflicting classifications of pathogenicity Condition: not provided
Costello syndrome		 Criteria Provided
Conflicting Classifications
 CA5779227 rs_370181298

2 SubmittersRCV000681281RCV001078758
NM_005343.4(HRAS):c.302A>G (p.Lys101Arg) SNV
Germline		 Chr11:533601 Conflicting classifications of pathogenicity Condition: not provided
Costello syndrome		 Criteria Provided
Conflicting Classifications
 CA378923959 rs_1131691997

2 SubmittersRCV000494039RCV000705122
NM_005343.4(HRAS):c.451-5C>T SNV
Germline		 Chr11:532760 Conflicting classifications of pathogenicity Costello syndrome
Condition: not provided
Cardiovascular phenotype		 Criteria Provided
Conflicting Classifications
 CA5779228 rs_370181298

3 SubmittersRCV000637310RCV001698422RCV004024985
NM_005343.4(HRAS):c.397C>T (p.Leu133Phe) SNV
Germline		 Chr11:533506 Conflicting classifications of pathogenicity Costello syndrome
Cardiovascular phenotype		 Criteria Provided
Conflicting Classifications
 CA5779321 rs_776888712

2 SubmittersRCV000637303RCV002358789
NM_005343.4(HRAS):c.137T>C (p.Ile46Thr) SNV
Germline		 Chr11:533919 Conflicting classifications of pathogenicity Condition: not provided
Costello syndrome		 Criteria Provided
Conflicting Classifications
 CA378924769 rs_1564789700

2 SubmittersRCV000681108RCV001861890
NM_005343.4(HRAS):c.394G>A (p.Asp132Asn) SNV
Germline		 Chr11:533509 Conflicting classifications of pathogenicity Costello syndrome
Condition: not provided
not specified
Intellectual disability		 Criteria Provided
Conflicting Classifications
 CA5779322 rs_759893630

4 SubmittersRCV000687312RCV000788501RCV004782512RCV005626154
NM_005343.4(HRAS):c.388G>C (p.Ala130Pro) SNV
Germline		 Chr11:533515 Conflicting classifications of pathogenicity Costello syndrome Criteria Provided
Conflicting Classifications
 CA378923024 rs_1564788957

2 SubmittersRCV000707594
NM_005343.4(HRAS):c.178G>A (p.Gly60Ser) SNV
Germline		 Chr11:533878 Likely pathogenic Costello syndrome Criteria Provided
Single Submitter
 CA378924681 rs_1589792804

1 SubmittersRCV000818197
NM_005343.4(HRAS):c.102C>G (p.Pro34=) SNV
Germline		 Chr11:534221 Conflicting classifications of pathogenicity Condition: not provided
Costello syndrome		 Criteria Provided
Conflicting Classifications
 CA472429377 rs_149199691

3 SubmittersRCV000868366RCV001493838
NM_005343.4(HRAS):c.491G>A (p.Arg164Gln) SNV
Germline		 Chr11:532715 Conflicting classifications of pathogenicity Costello syndrome
Condition: not provided
HRAS-related disorder		 Criteria Provided
Conflicting Classifications
 CA5779218 rs_753977266

4 SubmittersRCV001219438RCV001776147RCV003398958
NM_005343.4(HRAS):c.112-13T>A SNV
Germline		 Chr11:533957 Conflicting classifications of pathogenicity not specified
Condition: not provided
Costello syndrome		 Criteria Provided
Conflicting Classifications
 CA5779400 rs_766582484

3 SubmittersRCV001269170RCV001683760RCV002069390
NM_005343.4(HRAS):c.386A>G (p.Gln129Arg) SNV
Germline		 Chr11:533517 Conflicting classifications of pathogenicity Costello syndrome
not specified
HRAS-related disorder		 Criteria Provided
Conflicting Classifications
 CA378923040 rs_1851242529

4 SubmittersRCV001329395RCV005419086RCV005225372
NM_005343.4(HRAS):c.361G>A (p.Ala121Thr) SNV
Germline		 Chr11:533542 Conflicting classifications of pathogenicity Costello syndrome
Ovarian cancer		 Criteria Provided
Conflicting Classifications
 CA378923349 rs_1851245429

2 SubmittersRCV001338691RCV003153999
NM_005343.4(HRAS):c.261C>T (p.Thr87=) SNV
Germline		 Chr11:533795 Conflicting classifications of pathogenicity Costello syndrome
Cardiovascular phenotype
Condition: not provided		 Criteria Provided
Conflicting Classifications
 CA472429234 rs_1851272766

3 SubmittersRCV001415096RCV002456666RCV004801008
NM_176795.5(HRAS):c.481G>A (p.Gly161Arg) SNV
Germline		 Chr11:533328 Conflicting classifications of pathogenicity Condition: not provided
Costello syndrome		 Criteria Provided
Conflicting Classifications
 CA5779264 rs_750721065

3 SubmittersRCV003238053RCV005095098
NM_005343.4(HRAS):c.466T>C (p.Phe156Leu) SNV
Germline		 Chr11:532740 Pathogenic Costello syndrome Criteria Provided
Single Submitter
 CA378921204 rs_2133982557

1 SubmittersRCV001789705
NM_005343.4(HRAS):c.202C>T (p.Arg68Trp) SNV
Germline		 Chr11:533854 Conflicting classifications of pathogenicity Costello syndrome
Condition: not provided		 Criteria Provided
Conflicting Classifications
 CA378924631 rs_1370690781

2 SubmittersRCV001906898RCV003235615
NM_005343.4(HRAS):c.21G>C (p.Val7=) SNV
Germline		 Chr11:534302 Conflicting classifications of pathogenicity Cardiovascular phenotype
Condition: not provided
Costello syndrome		 Criteria Provided
Conflicting Classifications
 CA472322562 rs_1851321186

3 SubmittersRCV002425716RCV002466758RCV003098707
NM_005343.4(HRAS):c.122G>A (p.Arg41Gln) SNV
Germline		 Chr11:533934 Conflicting classifications of pathogenicity Costello syndrome Criteria Provided
Conflicting Classifications
 CA378924802 rs_868439179

2 SubmittersRCV003515838
NM_005343.4(HRAS):c.68T>G (p.Leu23Arg) SNV
Germline		 Chr11:534255 Likely pathogenic Costello syndrome Criteria Provided
Single Submitter

1 SubmittersRCV005255547
NM_004333.6(BRAF):c.1082A>T (p.Asp361Val) SNV
Germline		 Chr7:140794366 Likely pathogenic Costello syndrome Criteria Provided
Single Submitter

1 SubmittersRCV005623134