Total 18 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	Breast adenocarcinoma OVARIAN CANCER, EPITHELIAL, SOMATIC Carcinoma of colon Hepatocellular carcinoma Non-small cell lung carcinoma Seborrheic keratosis CLOVES syndrome Neoplasm of ovary PIK3CA related overgrowth syndrome Malignant melanoma of skin Ovarian serous cystadenocarcinoma Neoplasm of uterine cervix Pancreatic adenocarcinoma Brainstem glioma Squamous cell lung carcinoma Medulloblastoma Lung adenocarcinoma Neoplasm of the large intestine Transitional cell carcinoma of the bladder Uterine carcinosarcoma Adrenal cortex carcinoma Malignant neoplasm of body of uterus Glioblastoma Neoplasm of brain Papillary renal cell carcinoma type 1 Carcinoma of esophagus Breast neoplasm Neoplasm Squamous cell carcinoma of the head and neck Gastric adenocarcinoma Prostate adenocarcinoma Rosette-forming glioneuronal tumor MACRODACTYLY, SOMATIC Condition: not provided Lip and oral cavity carcinoma Abnormal cardiovascular system morphology Congenital macrodactylia Megalencephaly-capillary malformation-polymicrogyria syndrome Segmental undergrowth associated with mainly venous malformation with capillary component Segmental undergrowth associated with lymphatic malformation CEREBRAL CAVERNOUS MALFORMATIONS 4, SOMATIC CLAPO syndrome Cerebrofacial Vascular Metameric Syndrome (CVMS) Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes Breast carcinoma Gastric cancer Klippel-Trenaunay-like-Syndrome Rare venous malformation Rare combined vascular malformation	Reviewed By Expert Panel	CA123326	rs_121913279	27 SubmittersRCV000014622 RCV000014623 RCV000014624 RCV000014626 RCV000014627 RCV000014628 RCV000024621 RCV000154516 RCV000201231 RCV000419938 RCV000432506 RCV000442164 RCV000420562 RCV000426498 RCV000426614 RCV000421855 RCV000422442 RCV000437153 RCV000428372 RCV000425956 RCV000431232 RCV000430589 RCV000442731 RCV000432543 RCV000433127 RCV000437782 RCV000436234 RCV000438435 RCV000437287 RCV000443546 RCV000442736 RCV000487449 RCV000709691 RCV001092442 RCV001255686 RCV001327968 RCV001526648 RCV001807727 RCV001705589 RCV001705590 RCV001728091 RCV001729349 RCV001730472 RCV001836707 RCV003128082 RCV002508124 RCV003325939 RCV004527290 RCV004527291
NM_006218.4(PIK3CA):c.3140A>T (p.His1047Leu)	SNV Germline/somatic	Chr3:179234297	Pathogenic	Breast adenocarcinoma CLOVES syndrome PIK3CA related overgrowth syndrome Pancreatic adenocarcinoma Transitional cell carcinoma of the bladder Uterine carcinosarcoma Neoplasm of the large intestine Neoplasm of uterine cervix Breast neoplasm Gastric adenocarcinoma Medulloblastoma Prostate adenocarcinoma Squamous cell lung carcinoma Papillary renal cell carcinoma type 1 Neoplasm of ovary Malignant melanoma of skin Brainstem glioma Malignant neoplasm of body of uterus Neoplasm of brain Ovarian serous cystadenocarcinoma Lung adenocarcinoma Squamous cell carcinoma of the head and neck Hepatocellular carcinoma Carcinoma of esophagus Non-small cell lung carcinoma Adrenal cortex carcinoma Glioblastoma CLAPO syndrome Stroke disorder Macrodactyly of toe Cowden syndrome 1 Hemihypertrophy Megalencephaly-capillary malformation-polymicrogyria syndrome Colorectal cancer CEREBRAL CAVERNOUS MALFORMATIONS 4, SOMATIC Condition: not provided Cavernous lymphangioma	Criteria Provided Multiple Submitters No Conflicts	CA123328	rs_121913279	12 SubmittersRCV000014629 RCV000032905 RCV000201235 RCV000417557 RCV000429614 RCV000433765 RCV000438270 RCV000439524 RCV000440269 RCV000443341 RCV000418190 RCV000418315 RCV000423706 RCV000425496 RCV000422323 RCV000424813 RCV000442340 RCV000434874 RCV000443510 RCV000435425 RCV000435543 RCV000423048 RCV000427278 RCV000427664 RCV000428229 RCV000428866 RCV000434398 RCV000709692 RCV000626894 RCV000987367 RCV001526597 RCV001253236 RCV001807728 RCV001728092 RCV002254265 RCV004527292
NM_006218.4(PIK3CA):c.1633G>A (p.Glu545Lys)	SNV Germline/somatic	Chr3:179218303	Pathogenic/Likely pathogenic	Breast adenocarcinoma OVARIAN CANCER, EPITHELIAL, SOMATIC Carcinoma of colon Seborrheic keratosis Non-small cell lung carcinoma Megalencephaly-capillary malformation-polymicrogyria syndrome Sarcoma Squamous cell carcinoma of the head and neck Papillary renal cell carcinoma type 1 Neoplasm of ovary Ovarian serous cystadenocarcinoma Small cell lung carcinoma Glioblastoma Gastric adenocarcinoma Uterine carcinosarcoma Squamous cell lung carcinoma Prostate adenocarcinoma Pancreatic adenocarcinoma Carcinoma of esophagus Transitional cell carcinoma of the bladder Nasopharyngeal neoplasm Hepatocellular carcinoma Malignant neoplasm of body of uterus Neoplasm of uterine cervix Gallbladder carcinoma Neoplasm of the large intestine Breast neoplasm Malignant melanoma of skin Papillary renal cell carcinoma, sporadic Brainstem glioma Lung adenocarcinoma Neoplasm of brain Condition: not provided CLOVES syndrome PIK3CA related overgrowth syndrome Segmental undergrowth associated with lymphatic malformation Gallbladder cancer Abnormal cardiovascular system morphology Eccrine Angiomatous Hamartoma Cerebrofacial Vascular Metameric Syndrome (CVMS) HEMIFACIAL MYOHYPERPLASIA, SOMATIC Gastric cancer Angioosteohypertrophic syndrome Rare venous malformation Rare combined vascular malformation	Criteria Provided Multiple Submitters No Conflicts	CA123334	rs_104886003	19 SubmittersRCV000014631 RCV000014632 RCV000014633 RCV000014636 RCV000038671 RCV000055930 RCV000119356 RCV000421583 RCV000421958 RCV000422210 RCV000426520 RCV000433976 RCV000438445 RCV000440694 RCV000441866 RCV000418058 RCV000417835 RCV000420851 RCV000423327 RCV000427202 RCV000428639 RCV000437876 RCV000425490 RCV000429391 RCV000438060 RCV000438587 RCV000431416 RCV000432636 RCV000433152 RCV000441949 RCV000440053 RCV000442569 RCV001092440 RCV001262721 RCV001290591 RCV001705591 RCV001374447 RCV001327963 RCV001786329 RCV001730473 RCV003764575 RCV002508125 RCV004527293 RCV004527294 RCV004527295
NM_006218.4(PIK3CA):c.1624G>A (p.Glu542Lys)	SNV Germline/somatic	Chr3:179218294	Pathogenic	CLOVES syndrome Neoplasm of ovary Non-small cell lung carcinoma Condition: not provided Small cell lung carcinoma Neoplasm of the large intestine Squamous cell lung carcinoma Transitional cell carcinoma of the bladder Lung adenocarcinoma Breast neoplasm Carcinoma of esophagus Malignant neoplasm of body of uterus Gastric adenocarcinoma Prostate adenocarcinoma Neoplasm of brain Glioblastoma Squamous cell carcinoma of the head and neck Neoplasm of uterine cervix Papillary renal cell carcinoma, sporadic Hepatocellular carcinoma 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 Cowden syndrome PIK3CA-related overgrowth PIK3CA-related disorder PIK3CA related overgrowth syndrome HEMIFACIAL MYOHYPERPLASIA, SOMATIC Rare venous malformation	Reviewed By Expert Panel	CA333572	rs_121913273	17 SubmittersRCV000024622 RCV000151649 RCV000154513 RCV000416776 RCV000431000 RCV000431872 RCV000436932 RCV000438815 RCV000441707 RCV000442348 RCV000419905 RCV000420078 RCV000419440 RCV000426691 RCV000421639 RCV000433007 RCV000425548 RCV000430763 RCV000435811 RCV000445059 RCV000709693 RCV001255687 RCV001728093 RCV001327962 RCV001730477 RCV001836714 RCV002513230 RCV003987334 RCV004532404 RCV003458190 RCV003764635 RCV004527296
NM_006218.4(PIK3CA):c.1258T>C (p.Cys420Arg)	SNV Germline/somatic	Chr3:179210192	Pathogenic	CLOVES syndrome PIK3CA related overgrowth syndrome Neoplasm of ovary Squamous cell lung carcinoma Prostate adenocarcinoma Adenoid cystic carcinoma Gastric adenocarcinoma Malignant neoplasm of body of uterus Breast neoplasm Neoplasm of the large intestine CLAPO syndrome Abnormal cardiovascular system morphology Capillary malformation Segmental undergrowth associated with lymphatic malformation Condition: not provided Rare combined vascular malformation Cowden syndrome	Criteria Provided Multiple Submitters No Conflicts	CA180900	rs_121913272	15 SubmittersRCV000024623 RCV000201232 RCV000154512 RCV000444813 RCV000423306 RCV000427443 RCV000434659 RCV000444019 RCV000433143 RCV000439612 RCV000709694 RCV001327960 RCV001526612 RCV001705599 RCV002054475 RCV004527297 RCV003588566
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 Gastric adenocarcinoma Lung adenocarcinoma Ovarian serous cystadenocarcinoma Neoplasm of the large intestine Adrenal cortex carcinoma Malignant neoplasm of body of uterus Squamous cell lung carcinoma Malignant melanoma of skin Brainstem glioma Squamous cell carcinoma of the head and neck Pancreatic adenocarcinoma Hepatocellular carcinoma Malignant tumor of floor of mouth Glioblastoma Transitional cell carcinoma of the bladder Cowden syndrome Medulloblastoma Prostate adenocarcinoma Neoplasm of brain Carcinoma of esophagus Uterine carcinosarcoma Neoplasm of uterine cervix Breast neoplasm Papillary renal cell carcinoma type 1 13 conditions Condition: not provided Segmental undergrowth associated with mainly venous malformation with capillary component CLOVES syndrome PIK3CA related overgrowth syndrome HEMIFACIAL MYOHYPERPLASIA, SOMATIC	Criteria Provided Multiple Submitters No Conflicts	CA130471	rs_121913281	13 SubmittersRCV000032909 RCV000038675 RCV000425119 RCV000432323 RCV000436090 RCV000441963 RCV000444680 RCV000423369 RCV000425540 RCV000425809 RCV000435399 RCV000440398 RCV000441716 RCV000418438 RCV000420550 RCV000428005 RCV000435124 RCV000698423 RCV000417782 RCV000422744 RCV000424877 RCV000430750 RCV000432906 RCV000433635 RCV000441028 RCV000442782 RCV000763508 RCV001092441 RCV001705625 RCV002226661 RCV003233079 RCV003882732
NM_006218.4(PIK3CA):c.1252G>A (p.Glu418Lys)	SNV Germline/somatic	Chr3:179210186	Conflicting classifications of pathogenicity	not specified CLOVES syndrome PIK3CA related overgrowth syndrome PIK3CA-related disorder	Criteria Provided Conflicting Classifications	CA136365	rs_397517199	4 SubmittersRCV000038669 RCV001256198 RCV003458192 RCV004534818
NM_006218.4(PIK3CA):c.3073A>G (p.Thr1025Ala)	SNV Germline/somatic	Chr3:179234230	Pathogenic/Likely pathogenic	Non-small cell lung carcinoma CLOVES syndrome Condition: not provided PIK3CA related overgrowth syndrome	Criteria Provided Multiple Submitters No Conflicts	CA136374	rs_397517202	5 SubmittersRCV000038673 RCV001526503 RCV002254274 RCV003458194
NM_006218.4(PIK3CA):c.1357G>A (p.Glu453Lys)	SNV Germline/somatic	Chr3:179210291	Pathogenic	Gastric adenocarcinoma Glioblastoma Neoplasm of brain Squamous cell carcinoma of the head and neck Hepatocellular carcinoma Malignant neoplasm of body of uterus Breast neoplasm Squamous cell lung carcinoma Lung adenocarcinoma Transitional cell carcinoma of the bladder Neoplasm of ovary Megalencephaly-capillary malformation-polymicrogyria syndrome Abnormal cardiovascular system morphology CLOVES syndrome Condition: not provided Cowden syndrome PIK3CA-related disorder PIK3CA related overgrowth syndrome	Criteria Provided Multiple Submitters No Conflicts	CA16602904	rs_1057519925	12 SubmittersRCV000422944 RCV000425038 RCV000434215 RCV000440626 RCV000442682 RCV000443243 RCV000423945 RCV000430361 RCV000433137 RCV000435327 RCV000785580 RCV000991209 RCV001327961 RCV001526693 RCV001775789 RCV001861479 RCV002244865 RCV002472374
NM_006218.4(PIK3CA):c.241G>A (p.Glu81Lys)	SNV Germline/somatic	Chr3:179199066	Pathogenic	Malignant neoplasm of body of uterus Neoplasm of uterine cervix Squamous cell carcinoma of the head and neck Papillary renal cell carcinoma type 1 Lung adenocarcinoma Neoplasm of the large intestine Medulloblastoma Glioblastoma Breast neoplasm CLOVES syndrome Megalencephaly-capillary malformation-polymicrogyria syndrome Condition: not provided Abnormal cardiovascular system morphology PIK3CA related overgrowth syndrome Cowden syndrome	Criteria Provided Multiple Submitters No Conflicts	CA16602912	rs_1057519929	8 SubmittersRCV000419439 RCV000418157 RCV000420013 RCV000430702 RCV000438199 RCV000438786 RCV000426861 RCV000431022 RCV000436699 RCV001526599 RCV001542570 RCV001837893 RCV001327958 RCV003458199 RCV002524695
NM_006218.4(PIK3CA):c.317G>T (p.Gly106Val)	SNV Germline/somatic	Chr3:179199142	Conflicting classifications of pathogenicity	Uterine carcinosarcoma Neoplasm of the large intestine Transitional cell carcinoma of the bladder Neoplasm of uterine cervix Malignant neoplasm of body of uterus Squamous cell lung carcinoma Cowden syndrome CLOVES syndrome	Criteria Provided Conflicting Classifications	CA16602913	rs_1057519930	3 SubmittersRCV000422256 RCV000422135 RCV000432967 RCV000439354 RCV000438620 RCV000427943 RCV000631208 RCV001526649
NM_002067.5(GNA11):c.547C>T (p.Arg183Cys)	SNV Somatic	Chr19:3115014	Pathogenic	Lobular capillary hemangiomas Condition: not provided Segmental undergrowth associated with capillary malformation CLOVES syndrome Capillary malformation	Criteria Provided Multiple Submitters No Conflicts		rs_1555702147	5 SubmittersRCV000662311 RCV002254302 RCV001706699 RCV001526637 RCV001526569
NM_006218.4(PIK3CA):c.1132T>C (p.Cys378Arg)	SNV Somatic	Chr3:179204575	Pathogenic	Klippel-TrÃ©naunay syndrome CLOVES syndrome Megalencephaly-capillary malformation-polymicrogyria syndrome Capillary malformation	Criteria Provided Multiple Submitters No Conflicts		rs_1724507777	4 SubmittersRCV001265073 RCV001526537 RCV003225150 RCV003485684
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		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			1 SubmittersRCV003990433