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) Segmental undergrowth associated with mainly venous malformation with capillary component Segmental undergrowth associated with lymphatic malformation Megalencephaly-capillary malformation-polymicrogyria syndrome Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes Congenital macrodactylia Gastric cancer Breast carcinoma Klippel-Trenaunay-like-Syndrome Rare venous malformation Rare combined vascular malformation PIK3CA-related disorder PIK3CA-Related Overgrowth Spectrum Disorders	Reviewed By Expert Panel	CA123326	rs_121913279	30 SubmittersRCV000014624 RCV000014626 RCV000014627 RCV000014628 RCV000014622 RCV000014623 RCV000024621 RCV000154516 RCV000201231 RCV000438435 RCV000487449 RCV000709691 RCV001092442 RCV001255686 RCV001327968 RCV001728091 RCV001729349 RCV001730472 RCV001705589 RCV001705590 RCV001807727 RCV001836707 RCV001526648 RCV002508124 RCV003128082 RCV003325939 RCV004527290 RCV004527291 RCV004737153 RCV005051734
NM_006218.4(PIK3CA):c.3140A>T (p.His1047Leu)	SNV Germline/somatic	Chr3:179234297	Pathogenic	Breast adenocarcinoma PIK3CA related overgrowth syndrome CLOVES syndrome Stroke disorder Macrodactyly of toe Ovarian neoplasm CLAPO syndrome Cowden syndrome 1 Megalencephaly-capillary malformation-polymicrogyria syndrome CEREBRAL CAVERNOUS MALFORMATIONS 4, SOMATIC Hemihypertrophy Condition: not provided Colorectal cancer Cavernous lymphangioma Neoplasm Inborn genetic diseases	Criteria Provided Multiple Submitters No Conflicts	CA123328	rs_121913279	13 SubmittersRCV000014629 RCV000201235 RCV000032905 RCV000626894 RCV000422323 RCV000709692 RCV000987367 RCV001253236 RCV001728092 RCV001526597 RCV002254265 RCV001807728 RCV004527292 RCV004668728 RCV004649064
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 CLOVES syndrome Abnormal cardiovascular system morphology PIK3CA related overgrowth syndrome Cerebrofacial Vascular Metameric Syndrome (CVMS) 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	Criteria Provided Multiple Submitters No Conflicts	CA123334	rs_104886003	19 SubmittersRCV000014633 RCV000014636 RCV000014631 RCV000014632 RCV000038671 RCV000055930 RCV000119356 RCV000422210 RCV001092440 RCV001262721 RCV001327963 RCV001290591 RCV001730473 RCV001705591 RCV001374447 RCV001786329 RCV002508125 RCV003764575 RCV004527293 RCV004527294 RCV004527295 RCV004668729 RCV004698419
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 CEREBRAL CAVERNOUS MALFORMATIONS 4, SOMATIC Abnormal cardiovascular system morphology Cerebrofacial Vascular Metameric Syndrome (CVMS) Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes PIK3CA-related overgrowth PIK3CA-related disorder Cowden syndrome Megalencephaly-capillary malformation-polymicrogyria syndrome HEMIFACIAL MYOHYPERPLASIA, SOMATIC Rare venous malformation PIK3CA related overgrowth syndrome Neoplasm	Reviewed By Expert Panel	CA333572	rs_121913273	18 SubmittersRCV000024622 RCV000151649 RCV000154513 RCV000416776 RCV000709693 RCV001255687 RCV001728093 RCV001327962 RCV001730477 RCV001836714 RCV003987334 RCV004532404 RCV002513230 RCV004698785 RCV003764635 RCV004527296 RCV003458190 RCV004668742
NM_006218.4(PIK3CA):c.1258T>C (p.Cys420Arg)	SNV Germline/somatic	Chr3:179210192	Pathogenic	CLOVES syndrome PIK3CA related overgrowth syndrome Ovarian neoplasm CLAPO syndrome Abnormal cardiovascular system morphology Capillary malformation Rare combined vascular malformation Segmental undergrowth associated with lymphatic malformation Colorectal cancer Condition: not provided Cowden syndrome Neoplasm	Criteria Provided Multiple Submitters No Conflicts	CA180900	rs_121913272	16 SubmittersRCV000024623 RCV000201232 RCV000154512 RCV000709694 RCV001327960 RCV001526612 RCV004527297 RCV001705599 RCV005603590 RCV002054475 RCV003588566 RCV004668743
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 Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes PIK3CA related overgrowth syndrome Cowden syndrome 5 CLOVES syndrome PIK3CA-related disorder Inborn genetic diseases PIK3C1-related disorder Cowden syndrome Angioosteohypertrophic syndrome Abnormal cerebral morphology	Reviewed By Expert Panel	CA130467	rs_587776932	21 SubmittersRCV000032907 RCV000414672 RCV001327966 RCV001836717 RCV003233078 RCV001594376 RCV004798751 RCV004737167 RCV004955261 RCV005222712 RCV001852661 RCV002254272 RCV002274888
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 PIK3CA related overgrowth syndrome CLOVES syndrome HEMIFACIAL MYOHYPERPLASIA, SOMATIC PIK3CA overgrowth syndrome Inborn genetic diseases	Criteria Provided Multiple Submitters No Conflicts	CA130471	rs_121913281	14 SubmittersRCV000032909 RCV000038675 RCV000698423 RCV000763508 RCV001092441 RCV001705625 RCV003233079 RCV002226661 RCV003882732 RCV004698336 RCV004955262
NM_006218.4(PIK3CA):c.1252G>A (p.Glu418Lys)	SNV Germline/somatic	Chr3:179210186	Pathogenic	not specified CLOVES syndrome Neoplasm PIK3CA related overgrowth syndrome PIK3CA-related disorder	Criteria Provided Single Submitter	CA136365	rs_397517199	5 SubmittersRCV000038669 RCV001256198 RCV004668761 RCV003458192 RCV004534818
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 Cowden syndrome 5 Neoplasm CLOVES syndrome	Criteria Provided Multiple Submitters No Conflicts	CA16602516	rs_121913287	11 SubmittersRCV000785354 RCV001224952 RCV001562650 RCV002274026 RCV002275002 RCV003225067 RCV003995942 RCV004668930 RCV004767253
NM_006218.4(PIK3CA):c.1357G>A (p.Glu453Lys)	SNV Germline/somatic	Chr3:179210291	Pathogenic	Ovarian neoplasm Megalencephaly-capillary malformation-polymicrogyria syndrome CLOVES syndrome Abnormal cardiovascular system morphology Condition: not provided Cowden syndrome PIK3CA-related disorder PIK3CA related overgrowth syndrome	Criteria Provided Multiple Submitters No Conflicts	CA16602904	rs_1057519925	13 SubmittersRCV000785580 RCV000991209 RCV001526693 RCV001327961 RCV001775789 RCV001861479 RCV002244865 RCV002472374
NM_006218.4(PIK3CA):c.241G>A (p.Glu81Lys)	SNV Germline/somatic	Chr3:179199066	Pathogenic	Abnormal cardiovascular system morphology Megalencephaly-capillary malformation-polymicrogyria syndrome CLOVES syndrome Condition: not provided Cowden syndrome PIK3CA related overgrowth syndrome Neoplasm	Criteria Provided Multiple Submitters No Conflicts	CA16602912	rs_1057519929	8 SubmittersRCV001327958 RCV001542570 RCV001526599 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 Capillary malformation Segmental undergrowth associated with capillary malformation Condition: not provided CLOVES syndrome	Criteria Provided Conflicting Classifications	CA403307977	rs_1555702147	8 SubmittersRCV000662311 RCV001526569 RCV001706699 RCV002254302 RCV001526637
NM_006218.4(PIK3CA):c.1132T>C (p.Cys378Arg)	SNV Somatic	Chr3:179204575	Pathogenic	Klippel-TrÃ©naunay syndrome CLOVES syndrome Capillary malformation Megalencephaly-capillary malformation-polymicrogyria syndrome	Criteria Provided Multiple Submitters No Conflicts	CA355283139	rs_1724507777	4 SubmittersRCV001265073 RCV001526537 RCV003485684 RCV003225150
NM_181523.3(PIK3R1):c.1699A>G (p.Lys567Glu)	SNV Germline/somatic	Chr5:68295278	Likely pathogenic	Vascular Malformations and Overgrowth CLOVES syndrome	Criteria Provided Single Submitter	CA359883057	rs_1747645807	2 SubmittersRCV001290353 RCV002226776
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