Total 20 pathogenic variants reported for CLOVES syndrome

Variant Name	Variant Type	Variant Genomic Location	Clinical Significance	Phenotype Condition	Review Status	ClinGen Allele	dbSNP ID	Variation/condition record
NM_006218.4(PIK3CA):c.3140A>G (p.His1047Arg)	SNV Germline/somatic	Chr3:179234297	Pathogenic	Carcinoma of colon Hepatocellular carcinoma Non-small cell lung carcinoma Seborrheic keratosis Breast adenocarcinoma OVARIAN CANCER, EPITHELIAL, SOMATIC CLOVES syndrome Ovarian neoplasm PIK3CA related overgrowth syndrome Neoplasm Rosette-forming glioneuronal tumor MACRODACTYLY, SOMATIC Condition: not provided Lip and oral cavity carcinoma Abnormal cardiovascular system morphology CEREBRAL CAVERNOUS MALFORMATIONS 4, SOMATIC CLAPO syndrome Cerebrofacial Vascular Metameric Syndrome (CVMS) Megalencephaly-capillary malformation-polymicrogyria syndrome Congenital macrodactylia Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes Segmental undergrowth associated with mainly venous malformation with capillary component Segmental undergrowth associated with lymphatic malformation Gastric cancer Breast carcinoma Klippel-Trenaunay-like-Syndrome Rare venous malformation PIK3CA-related disorder Rare combined vascular malformation PIK3CA-Related Overgrowth Spectrum Disorders Nasopharyngeal carcinoma Diffuse midline glioma, H3 K27M-mutant Cervical squamous cell carcinoma Diffuse glioma, H3 G34 mutant Glioma Neuroblastoma Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype Colorectal cancer Adenoid cystic carcinoma Cavernous lymphangioma Embryonal rhabdomyosarcoma	Reviewed By Expert Panel	CA123326	rs_121913279	33 SubmittersRCV000014624 RCV000014626 RCV000014627 RCV000014628 RCV000014622 RCV000014623 RCV000024621 RCV000154516 RCV000201231 RCV000438435 RCV000487449 RCV000709691 RCV001092442 RCV001255686 RCV001327968 RCV001728091 RCV001729349 RCV001730472 RCV001807727 RCV001526648 RCV001836707 RCV001705589 RCV001705590 RCV002508124 RCV003128082 RCV003325939 RCV004527290 RCV004737153 RCV004527291 RCV005051734 RCV006253556 RCV006253562 RCV006456613 RCV006253564 RCV006253557 RCV006253555 RCV006253561 RCV006253558 RCV006253559 RCV006253563 RCV006253560
NM_006218.4(PIK3CA):c.3140A>T (p.His1047Leu)	SNV Germline/somatic	Chr3:179234297	Pathogenic	Breast adenocarcinoma CLOVES syndrome PIK3CA related overgrowth syndrome Ovarian neoplasm Stroke disorder Macrodactyly of toe CLAPO syndrome Cowden syndrome 1 Megalencephaly-capillary malformation-polymicrogyria syndrome Hemihypertrophy CEREBRAL CAVERNOUS MALFORMATIONS 4, SOMATIC Colorectal cancer Condition: not provided Cavernous lymphangioma Neoplasm Inborn genetic diseases Medulloblastoma WNT activated Rosette-forming glioneuronal tumor Diffuse midline glioma, H3 K27M-mutant	Criteria Provided Multiple Submitters No Conflicts	CA123328	rs_121913279	14 SubmittersRCV000014629 RCV000032905 RCV000201235 RCV000422323 RCV000626894 RCV000709692 RCV000987367 RCV001253236 RCV001526597 RCV001728092 RCV001807728 RCV002254265 RCV004527292 RCV004668728 RCV004649064 RCV006253567 RCV006253565 RCV006253566
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys)	SNV Germline/somatic	Chr3:179218303	Pathogenic/Likely pathogenic	Carcinoma of colon Seborrheic keratosis Breast adenocarcinoma OVARIAN CANCER, EPITHELIAL, SOMATIC Non-small cell lung carcinoma Megalencephaly-capillary malformation-polymicrogyria syndrome Sarcoma Ovarian neoplasm Condition: not provided Abnormal cardiovascular system morphology CLOVES syndrome Cerebrofacial Vascular Metameric Syndrome (CVMS) PIK3CA related overgrowth syndrome Segmental undergrowth associated with lymphatic malformation Gallbladder cancer Eccrine angiomatous hamartoma Gastric cancer HEMIFACIAL MYOHYPERPLASIA, SOMATIC Angioosteohypertrophic syndrome Rare venous malformation Rare combined vascular malformation Neoplasm PIK3CA overgrowth syndrome PIK3CA-related disorder Medulloblastoma WNT activated IDH-wildtype glioblastoma Rosette-forming glioneuronal tumor Cervical squamous cell carcinoma Adenocarcinoma of the large intestine Embryonal rhabdomyosarcoma Lymphatic malformation Congenital fibrosarcoma Cerebral cavernous malformation	Criteria Provided Multiple Submitters No Conflicts	CA123334	rs_104886003	22 SubmittersRCV000014633 RCV000014636 RCV000014631 RCV000014632 RCV000038671 RCV000055930 RCV000119356 RCV000422210 RCV001092440 RCV001327963 RCV001262721 RCV001730473 RCV001290591 RCV001705591 RCV001374447 RCV001786329 RCV002508125 RCV003764575 RCV004527293 RCV004527294 RCV004527295 RCV004668729 RCV004698419 RCV005867755 RCV006253573 RCV006253575 RCV006253570 RCV006456614 RCV006253574 RCV006253571 RCV006253569 RCV006253572 RCV006253568
NM_006218.4(PIK3CA):c.1624G>A (p.Glu542Lys)	SNV Germline/somatic	Chr3:179218294	Pathogenic	CLOVES syndrome Ovarian neoplasm Non-small cell lung carcinoma Condition: not provided CLAPO syndrome Lip and oral cavity carcinoma Cerebrofacial Vascular Metameric Syndrome (CVMS) CEREBRAL CAVERNOUS MALFORMATIONS 4, SOMATIC Abnormal cardiovascular system morphology Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes PIK3CA-related overgrowth PIK3CA related overgrowth syndrome PIK3CA-related disorder Rare venous malformation Cowden syndrome Megalencephaly-capillary malformation-polymicrogyria syndrome Neoplasm HEMIFACIAL MYOHYPERPLASIA, SOMATIC Rosette-forming glioneuronal tumor Alveolar rhabdomyosarcoma Diffuse midline glioma, H3 K27M-mutant Vascular malformation Glioma Cervical squamous cell carcinoma	Reviewed By Expert Panel	CA333572	rs_121913273	20 SubmittersRCV000024622 RCV000151649 RCV000154513 RCV000416776 RCV000709693 RCV001255687 RCV001730477 RCV001728093 RCV001327962 RCV001836714 RCV003987334 RCV003458190 RCV004532404 RCV004527296 RCV002513230 RCV004698785 RCV004668742 RCV003764635 RCV006253684 RCV006253682 RCV006253686 RCV006253685 RCV006253683 RCV006456623
NM_006218.4(PIK3CA):c.1258T>C (p.Cys420Arg)	SNV Germline/somatic	Chr3:179210192	Pathogenic	CLOVES syndrome Ovarian neoplasm PIK3CA related overgrowth syndrome CLAPO syndrome Abnormal cardiovascular system morphology Segmental undergrowth associated with lymphatic malformation Capillary malformation Condition: not provided Rare combined vascular malformation Cowden syndrome Neoplasm Colorectal cancer Neuroblastoma Medulloblastoma WNT activated IDH-wildtype glioblastoma Immature ovarian teratoma Colon adenocarcinoma PIK3CA-related disorder Diffuse midline glioma, H3 K27M-mutant	Criteria Provided Multiple Submitters No Conflicts	CA180900	rs_121913272	18 SubmittersRCV000024623 RCV000154512 RCV000201232 RCV000709694 RCV001327960 RCV001705599 RCV001526612 RCV002054475 RCV004527297 RCV003588566 RCV004668743 RCV005603590 RCV006253688 RCV006253690 RCV006253691 RCV006253692 RCV006253687 RCV005867798 RCV006253689
NM_006218.4(PIK3CA):c.2740G>A (p.Gly914Arg)	SNV Germline/somatic	Chr3:179230077	Pathogenic	Megalencephaly-capillary malformation-polymicrogyria syndrome Condition: not provided Abnormal cardiovascular system morphology Cowden syndrome 5 Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes Cowden syndrome Angioosteohypertrophic syndrome Abnormal cerebral morphology PIK3CA related overgrowth syndrome CLOVES syndrome PIK3CA-related disorder Inborn genetic diseases PIK3C1-related disorder	Reviewed By Expert Panel	CA130467	rs_587776932	21 SubmittersRCV000032907 RCV000414672 RCV001327966 RCV001594376 RCV001836717 RCV001852661 RCV002254272 RCV002274888 RCV003233078 RCV004798751 RCV004737167 RCV004955261 RCV005222712
NM_006218.4(PIK3CA):c.3139C>T (p.His1047Tyr)	SNV Germline/somatic	Chr3:179234296	Pathogenic	Megalencephaly-capillary malformation-polymicrogyria syndrome Non-small cell lung carcinoma Cowden syndrome 13 conditions Condition: not provided Segmental undergrowth associated with mainly venous malformation with capillary component CLOVES syndrome PIK3CA related overgrowth syndrome HEMIFACIAL MYOHYPERPLASIA, SOMATIC PIK3CA overgrowth syndrome Inborn genetic diseases Sialoblastoma Diffuse midline glioma, H3 K27M-mutant	Criteria Provided Multiple Submitters No Conflicts	CA130471	rs_121913281	15 SubmittersRCV000032909 RCV000038675 RCV000698423 RCV000763508 RCV001092441 RCV001705625 RCV002226661 RCV003233079 RCV003882732 RCV004698336 RCV004955262 RCV006253703 RCV006253702
NM_006218.4(PIK3CA):c.1252G>A (p.Glu418Lys)	SNV Germline/somatic	Chr3:179210186	Pathogenic	not specified CLOVES syndrome PIK3CA related overgrowth syndrome PIK3CA-related disorder Neoplasm	Criteria Provided Single Submitter	CA136365	rs_397517199	5 SubmittersRCV000038669 RCV001256198 RCV003458192 RCV004534818 RCV004668761
NM_006218.4(PIK3CA):c.3073A>G (p.Thr1025Ala)	SNV Germline/somatic	Chr3:179234230	Pathogenic/Likely pathogenic	Non-small cell lung carcinoma Condition: not provided PIK3CA related overgrowth syndrome CLOVES syndrome	Criteria Provided Multiple Submitters No Conflicts	CA136374	rs_397517202	5 SubmittersRCV000038673 RCV002254274 RCV003458194 RCV001526503
NM_006218.4(PIK3CA):c.263G>A (p.Arg88Gln)	SNV Germline/somatic	Chr3:179199088	Pathogenic	Ovarian neoplasm Cowden syndrome Condition: not provided PIK3CA related overgrowth syndrome Abnormal cerebral morphology Megalencephaly-capillary malformation-polymicrogyria syndrome Neoplasm CLOVES syndrome Cowden syndrome 5 Pilocytic astrocytoma Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype Medulloblastoma WNT activated Giant cell glioblastoma	Criteria Provided Multiple Submitters No Conflicts	CA16602516	rs_121913287	12 SubmittersRCV000785354 RCV001224952 RCV001562650 RCV002274026 RCV002275002 RCV003225067 RCV004668930 RCV004767253 RCV003995942 RCV006253972 RCV006253973 RCV006253974 RCV006253975
NM_006218.4(PIK3CA):c.1357G>A (p.Glu453Lys)	SNV Germline/somatic	Chr3:179210291	Pathogenic	Ovarian neoplasm Megalencephaly-capillary malformation-polymicrogyria syndrome Abnormal cardiovascular system morphology CLOVES syndrome Condition: not provided Cowden syndrome PIK3CA-related disorder PIK3CA related overgrowth syndrome Neoplasm	Criteria Provided Multiple Submitters No Conflicts	CA16602904	rs_1057519925	14 SubmittersRCV000785580 RCV000991209 RCV001327961 RCV001526693 RCV001775789 RCV001861479 RCV002244865 RCV002472374 RCV006273732
NM_006218.4(PIK3CA):c.241G>A (p.Glu81Lys)	SNV Germline/somatic	Chr3:179199066	Pathogenic	Abnormal cardiovascular system morphology CLOVES syndrome Megalencephaly-capillary malformation-polymicrogyria syndrome Condition: not provided Cowden syndrome PIK3CA related overgrowth syndrome Neoplasm	Criteria Provided Multiple Submitters No Conflicts	CA16602912	rs_1057519929	8 SubmittersRCV001327958 RCV001526599 RCV001542570 RCV001837893 RCV002524695 RCV003458199 RCV005230297
NM_006218.4(PIK3CA):c.317G>T (p.Gly106Val)	SNV Germline/somatic	Chr3:179199142	Conflicting classifications of pathogenicity	Cowden syndrome CLOVES syndrome PIK3CA related overgrowth syndrome	Criteria Provided Conflicting Classifications	CA16602913	rs_1057519930	3 SubmittersRCV000631208 RCV001526649 RCV004719813
NM_002067.5(GNA11):c.547C>T (p.Arg183Cys)	SNV Germline/somatic	Chr19:3115014	Conflicting classifications of pathogenicity	Lobular capillary hemangiomas CLOVES syndrome Capillary malformation Segmental undergrowth associated with capillary malformation Condition: not provided	Criteria Provided Conflicting Classifications	CA403307977	rs_1555702147	8 SubmittersRCV000662311 RCV001526637 RCV001526569 RCV001706699 RCV002254302
NM_006218.4(PIK3CA):c.1132T>C (p.Cys378Arg)	SNV Germline/somatic	Chr3:179204575	Pathogenic	CLOVES syndrome Capillary malformation Megalencephaly-capillary malformation-polymicrogyria syndrome Inborn genetic diseases Medulloblastoma WNT activated Angioosteohypertrophic syndrome	Criteria Provided Multiple Submitters No Conflicts	CA355283139	rs_1724507777	6 SubmittersRCV001526537 RCV003485684 RCV003225150 RCV005702427 RCV006254201 RCV006272147
NM_181523.3(PIK3R1):c.1699A>G (p.Lys567Glu)	SNV Germline/somatic	Chr5:68295278	Likely pathogenic	Vascular Malformations and Overgrowth CLOVES syndrome Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype	Criteria Provided Single Submitter	CA359883057	rs_1747645807	2 SubmittersRCV001290353 RCV002226776 RCV006254262
NM_006218.4(PIK3CA):c.813+2T>C	SNV Germline	Chr3:179201542	Likely pathogenic	CLOVES syndrome	Criteria Provided Single Submitter	CA355278641	rs_2108390250	1 SubmittersRCV003990433