Total 40 pathogenic variants reported for Myhre syndrome

Variant Name	Variant Type	Variant Genomic Location	Clinical Significance	Phenotype Condition	Review Status	ClinGen Allele	dbSNP ID	Variation/condition record
NM_005359.6(SMAD4):c.1082G>A (p.Arg361His)	SNV Germline/somatic	Chr18:51065549	Pathogenic/Likely pathogenic	Squamous cell carcinoma of the head and neck Breast neoplasm Neoplasm of uterine cervix Neoplasm of the large intestine Carcinoma of esophagus Pancreatic adenocarcinoma Lung adenocarcinoma Gastric adenocarcinoma Condition: not provided Juvenile polyposis syndrome Myhre syndrome Generalized juvenile polyposis/juvenile polyposis coli Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Carcinoma of pancreas Hereditary cancer-predisposing syndrome Familial thoracic aortic aneurysm and aortic dissection Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome	Criteria Provided Multiple Submitters No Conflicts	CA128097	rs_377767347	7 SubmittersRCV000421390 RCV000441473 RCV000419206 RCV000431203 RCV000423753 RCV000431590 RCV000434006 RCV000439037 RCV000520995 RCV000635423 RCV000763030 RCV002316201 RCV004018654
NM_005359.6(SMAD4):c.1499T>C (p.Ile500Thr)	SNV Germline	Chr18:51078307	Pathogenic	Myhre syndrome Condition: not provided Juvenile polyposis syndrome	Criteria Provided Multiple Submitters No Conflicts	CA128977	rs_281875321	11 SubmittersRCV000023060 RCV000059734 RCV001852006
NM_005359.6(SMAD4):c.1498A>G (p.Ile500Val)	SNV Germline	Chr18:51078306	Pathogenic	Myhre syndrome Condition: not provided Generalized juvenile polyposis/juvenile polyposis coli Myhre syndrome Generalized juvenile polyposis/juvenile polyposis coli Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Carcinoma of pancreas Myhre syndrome Generalized juvenile polyposis/juvenile polyposis coli Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Juvenile polyposis syndrome Intellectual disability Neurodevelopmental delay Hereditary cancer-predisposing syndrome Familial thoracic aortic aneurysm and aortic dissection	Criteria Provided Multiple Submitters No Conflicts	CA128979	rs_281875322	38 SubmittersRCV000023061 RCV000059733 RCV000635427 RCV000763031 RCV001249691 RCV001376590 RCV001260808 RCV001375955 RCV004558272
NM_005359.6(SMAD4):c.1500A>G (p.Ile500Met)	SNV Germline	Chr18:51078308	Pathogenic	Myhre syndrome Condition: not provided	No Assertion Criteria Provided	CA128981	rs_281875320	4 SubmittersRCV000023062 RCV000059735
NM_005359.6(SMAD4):c.1573A>G (p.Ile525Val)	SNV Germline	Chr18:51078381	Conflicting classifications of pathogenicity	Condition: not provided Generalized juvenile polyposis/juvenile polyposis coli Gastrointestinal polyposis not specified Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Myhre syndrome Hereditary cancer-predisposing syndrome Juvenile polyposis syndrome Familial thoracic aortic aneurysm and aortic dissection Hereditary cancer-predisposing syndrome Familial thoracic aortic aneurysm and aortic dissection	Criteria Provided Conflicting Classifications	CA211890	rs_149755320	27 SubmittersRCV000034710 RCV000123259 RCV000148889 RCV000213006 RCV000383039 RCV000327173 RCV000771070 RCV001420980 RCV001170612 RCV002310997
NM_005359.6(SMAD4):c.1486C>T (p.Arg496Cys)	SNV Germline	Chr18:51078294	Conflicting classifications of pathogenicity	Myhre syndrome Condition: not provided Moyamoya angiopathy Juvenile polyposis syndrome Hereditary cancer-predisposing syndrome Familial thoracic aortic aneurysm and aortic dissection Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Carcinoma of pancreas Myhre syndrome Juvenile polyposis syndrome Generalized juvenile polyposis/juvenile polyposis coli SMAD4-related disorder Hereditary cancer-predisposing syndrome	Criteria Provided Conflicting Classifications	CA145285	rs_397518413	26 SubmittersRCV000074360 RCV000160962 RCV001261800 RCV002228175 RCV002311544 RCV002483120 RCV000541839 RCV003398656 RCV003584539
NM_005359.6(SMAD4):c.424+5G>A	SNV Germline	Chr18:51048865	Conflicting classifications of pathogenicity	Hereditary cancer-predisposing syndrome not specified Generalized juvenile polyposis/juvenile polyposis coli Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Myhre syndrome Condition: not provided Familial thoracic aortic aneurysm and aortic dissection Familial thoracic aortic aneurysm and aortic dissection Hereditary cancer-predisposing syndrome Juvenile polyposis syndrome	Criteria Provided Conflicting Classifications	CA288122	rs_200772603	18 SubmittersRCV000115883 RCV000213004 RCV000204731 RCV000306889 RCV000346296 RCV000656977 RCV000770696 RCV002311002 RCV002228348
NM_005359.6(SMAD4):c.1653A>G (p.Leu551=)	SNV Germline	Chr18:51078461	Conflicting classifications of pathogenicity	Generalized juvenile polyposis/juvenile polyposis coli Hereditary cancer-predisposing syndrome not specified Myhre syndrome Juvenile polyposis syndrome Condition: not provided Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Familial thoracic aortic aneurysm and aortic dissection Hereditary cancer-predisposing syndrome SMAD4-related disorder	Criteria Provided Conflicting Classifications	CA186803	rs_199526820	11 SubmittersRCV000123261 RCV000162721 RCV000439984 RCV001125527 RCV001450073 RCV000858658 RCV001125528 RCV002310679 RCV003894971
NM_005359.6(SMAD4):c.671A>T (p.Gln224Leu)	SNV Germline	Chr18:51058128	Conflicting classifications of pathogenicity	Generalized juvenile polyposis/juvenile polyposis coli Condition: not provided Familial thoracic aortic aneurysm and aortic dissection Hereditary cancer-predisposing syndrome Juvenile polyposis syndrome Carcinoma of pancreas Myhre syndrome Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Juvenile polyposis syndrome SMAD4-related disorder Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Hereditary cancer-predisposing syndrome	Criteria Provided Conflicting Classifications	CA332851	rs_587780793	10 SubmittersRCV000123264 RCV000986028 RCV002310680 RCV001358798 RCV002483236 RCV003422007 RCV003315822 RCV003584556
NM_005359.6(SMAD4):c.1140-10T>C	SNV Germline	Chr18:51067009	Conflicting classifications of pathogenicity	not specified Condition: not provided Hereditary cancer-predisposing syndrome Generalized juvenile polyposis/juvenile polyposis coli Myhre syndrome Juvenile polyposis syndrome Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Myhre syndrome Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Juvenile polyposis syndrome Carcinoma of pancreas Hereditary cancer-predisposing syndrome Familial thoracic aortic aneurysm and aortic dissection	Criteria Provided Conflicting Classifications	CA293632	rs_186332162	15 SubmittersRCV000128173 RCV000586605 RCV000579485 RCV001080462 RCV001127536 RCV001507129 RCV001127535 RCV002492489 RCV002453458
NM_005359.6(SMAD4):c.1106A>G (p.Asn369Ser)	SNV Germline	Chr18:51065573	Conflicting classifications of pathogenicity	Hereditary cancer-predisposing syndrome Juvenile polyposis syndrome Condition: not provided Isolated thoracic aortic aneurysm Hereditary cancer-predisposing syndrome Familial thoracic aortic aneurysm and aortic dissection Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome not specified Myhre syndrome Carcinoma of pancreas Juvenile polyposis syndrome Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome	Criteria Provided Conflicting Classifications	CA167654	rs_139569694	12 SubmittersRCV000131130 RCV000555043 RCV000679584 RCV001374834 RCV002311018 RCV003474774 RCV004525878 RCV002478399
NM_005359.6(SMAD4):c.677C>T (p.Ala226Val)	SNV Germline	Chr18:51058134	Conflicting classifications of pathogenicity	Condition: not provided Generalized juvenile polyposis/juvenile polyposis coli Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Myhre syndrome Hereditary cancer-predisposing syndrome Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Carcinoma of pancreas Myhre syndrome Generalized juvenile polyposis/juvenile polyposis coli Juvenile polyposis syndrome Familial thoracic aortic aneurysm and aortic dissection Hereditary cancer-predisposing syndrome Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Myhre syndrome	Criteria Provided Conflicting Classifications	CA299961	rs_539739051	11 SubmittersRCV000160959 RCV000199953 RCV000260140 RCV000334040 RCV000449407 RCV000515353 RCV001420989 RCV002312690 RCV003483531
NM_005359.6(SMAD4):c.20C>T (p.Thr7Met)	SNV Germline	Chr18:51047066	Conflicting classifications of pathogenicity	Hereditary cancer-predisposing syndrome Generalized juvenile polyposis/juvenile polyposis coli Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Carcinoma of pancreas Myhre syndrome Generalized juvenile polyposis/juvenile polyposis coli Condition: not provided Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Juvenile polyposis syndrome Myhre syndrome Pulmonary arterial hypertension Familial thoracic aortic aneurysm and aortic dissection Hereditary cancer-predisposing syndrome not specified SMAD4-related disorder	Criteria Provided Conflicting Classifications	CA186263	rs_372316981	15 SubmittersRCV000162438 RCV000196213 RCV000764159 RCV000589285 RCV001123230 RCV001328507 RCV001123231 RCV002285148 RCV002310723 RCV002468936 RCV003398830
NM_005359.6(SMAD4):c.21G>A (p.Thr7=)	SNV Germline	Chr18:51047067	Conflicting classifications of pathogenicity	Hereditary cancer-predisposing syndrome Generalized juvenile polyposis/juvenile polyposis coli Condition: not provided Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Myhre syndrome Juvenile polyposis syndrome Hereditary cancer-predisposing syndrome Familial thoracic aortic aneurysm and aortic dissection not specified SMAD4-related disorder	Criteria Provided Conflicting Classifications	CA186871	rs_142292491	17 SubmittersRCV000162750 RCV000412290 RCV000760073 RCV001124331 RCV001124332 RCV001450081 RCV002310727 RCV002222413 RCV003927534
NM_005359.6(SMAD4):c.852A>G (p.Gln284=)	SNV Germline	Chr18:51058404	Conflicting classifications of pathogenicity	Hereditary cancer-predisposing syndrome Generalized juvenile polyposis/juvenile polyposis coli not specified Condition: not provided Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Myhre syndrome Juvenile polyposis syndrome Generalized juvenile polyposis/juvenile polyposis coli Hereditary hemorrhagic telangiectasia Familial thoracic aortic aneurysm and aortic dissection Hereditary cancer-predisposing syndrome	Criteria Provided Conflicting Classifications	CA186319	rs_144378484	13 SubmittersRCV000162465 RCV000200571 RCV000417748 RCV000589728 RCV001124423 RCV001124424 RCV001450056 RCV003330520 RCV002310724
NM_005359.6(SMAD4):c.736C>A (p.Pro246Thr)	SNV Germline	Chr18:51058193	Conflicting classifications of pathogenicity	Hereditary cancer-predisposing syndrome Generalized juvenile polyposis/juvenile polyposis coli Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Myhre syndrome Heritable Thoracic Aortic Disease Early age onset of sporadic thoracic aortic dissections Juvenile polyposis syndrome Condition: not provided Familial thoracic aortic aneurysm and aortic dissection Hereditary cancer-predisposing syndrome	Criteria Provided Conflicting Classifications	CA10580980	rs_876659967	7 SubmittersRCV000220373 RCV000689822 RCV001124420 RCV001123336 RCV000678043 RCV001261774 RCV001312210 RCV001762494 RCV002311325
NM_005359.6(SMAD4):c.342T>C (p.Tyr114=)	SNV Germline	Chr18:51048778	Conflicting classifications of pathogenicity	Generalized juvenile polyposis/juvenile polyposis coli not specified Hereditary cancer-predisposing syndrome Myhre syndrome Juvenile polyposis syndrome Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Familial thoracic aortic aneurysm and aortic dissection Hereditary cancer-predisposing syndrome	Criteria Provided Conflicting Classifications	CA8965768	rs_757211048	6 SubmittersRCV000227775 RCV000441778 RCV000571677 RCV001126992 RCV001450080 RCV001126991 RCV002311351
NM_005359.6(SMAD4):c.1644A>G (p.Pro548=)	SNV Germline	Chr18:51078452	Conflicting classifications of pathogenicity	Generalized juvenile polyposis/juvenile polyposis coli Myhre syndrome Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Hereditary cancer-predisposing syndrome not specified Juvenile polyposis syndrome Hereditary cancer-predisposing syndrome Familial thoracic aortic aneurysm and aortic dissection Condition: not provided SMAD4-related disorder	Criteria Provided Conflicting Classifications	CA8966112	rs_756795016	9 SubmittersRCV000226180 RCV000287385 RCV000340035 RCV000573053 RCV000613346 RCV001450069 RCV002311349 RCV003326381 RCV003967648
NM_005359.6(SMAD4):c.667+3G>A	SNV Germline	Chr18:51054996	Conflicting classifications of pathogenicity	Myhre syndrome Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Hereditary cancer-predisposing syndrome Generalized juvenile polyposis/juvenile polyposis coli Juvenile polyposis syndrome Condition: not provided Familial thoracic aortic aneurysm and aortic dissection Hereditary cancer-predisposing syndrome	Criteria Provided Conflicting Classifications	CA8965852	rs_757971589	8 SubmittersRCV000263575 RCV000358363 RCV000571451 RCV000635437 RCV001328519 RCV001711942 RCV002314055
NM_005359.6(SMAD4):c.-128+12A>G	SNV Germline	Chr18:51030635	Conflicting classifications of pathogenicity	Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Myhre syndrome Generalized juvenile polyposis/juvenile polyposis coli not specified	Criteria Provided Conflicting Classifications	CA10651749	rs_886053891	2 SubmittersRCV000267847 RCV000307763 RCV000362423 RCV000613032
NM_005359.6(SMAD4):c.249+10A>C	SNV Germline	Chr18:51047305	Conflicting classifications of pathogenicity	Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Generalized juvenile polyposis/juvenile polyposis coli Hereditary cancer-predisposing syndrome Myhre syndrome not specified Juvenile polyposis syndrome	Criteria Provided Conflicting Classifications	CA8965744	rs_752243771	6 SubmittersRCV000295030 RCV000409679 RCV000771622 RCV000389254 RCV000427458 RCV001450078
NM_005359.6(SMAD4):c.*30A>C	SNV Germline	Chr18:51078497	Conflicting classifications of pathogenicity	Generalized juvenile polyposis/juvenile polyposis coli Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Myhre syndrome	Criteria Provided Conflicting Classifications	CA8966118	rs_767288576	1 SubmittersRCV000298729 RCV000369760 RCV000399233
NM_005359.6(SMAD4):c.*1067G>A	SNV Germline	Chr18:51079534	Conflicting classifications of pathogenicity	Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Generalized juvenile polyposis/juvenile polyposis coli Myhre syndrome Condition: not provided	Criteria Provided Conflicting Classifications	CA10651763	rs_542839921	2 SubmittersRCV000261227 RCV000319786 RCV000372257 RCV003422294
NM_005359.6(SMAD4):c.876G>A (p.Pro292=)	SNV Germline	Chr18:51058428	Conflicting classifications of pathogenicity	not specified Hereditary cancer-predisposing syndrome Myhre syndrome Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Juvenile polyposis syndrome Generalized juvenile polyposis/juvenile polyposis coli Familial thoracic aortic aneurysm and aortic dissection Hereditary cancer-predisposing syndrome	Criteria Provided Conflicting Classifications	CA8965914	rs_753358186	6 SubmittersRCV000435398 RCV000579563 RCV001125428 RCV001125429 RCV001477273 RCV001125427 RCV002374637
NM_005359.6(SMAD4):c.1492T>C (p.Leu498=)	SNV Germline	Chr18:51078300	Conflicting classifications of pathogenicity	not specified Hereditary cancer-predisposing syndrome Condition: not provided Generalized juvenile polyposis/juvenile polyposis coli Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Juvenile polyposis syndrome Myhre syndrome Familial thoracic aortic aneurysm and aortic dissection Hereditary cancer-predisposing syndrome	Criteria Provided Conflicting Classifications	CA16608768	rs_1057520520	11 SubmittersRCV000427335 RCV000579788 RCV000679586 RCV001084748 RCV001123417 RCV001391325 RCV001123416 RCV002318979
NM_005359.6(SMAD4):c.1632G>A (p.Pro544=)	SNV Germline	Chr18:51078440	Conflicting classifications of pathogenicity	Generalized juvenile polyposis/juvenile polyposis coli Hereditary cancer-predisposing syndrome not specified Myhre syndrome Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Condition: not provided Juvenile polyposis syndrome Hereditary cancer-predisposing syndrome Familial thoracic aortic aneurysm and aortic dissection	Criteria Provided Conflicting Classifications	CA8966110	rs_549489716	9 SubmittersRCV000460479 RCV000564724 RCV000615584 RCV001124521 RCV001124520 RCV001284065 RCV001420984 RCV002311780
NM_005359.6(SMAD4):c.1545A>G (p.Arg515=)	SNV Germline	Chr18:51078353	Conflicting classifications of pathogenicity	Generalized juvenile polyposis/juvenile polyposis coli Hereditary cancer-predisposing syndrome not specified Myhre syndrome Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Juvenile polyposis syndrome Hereditary cancer-predisposing syndrome Familial thoracic aortic aneurysm and aortic dissection	Criteria Provided Conflicting Classifications	CA8966104	rs_760840557	6 SubmittersRCV000530327 RCV000581754 RCV000604219 RCV001123418 RCV001123419 RCV001391329 RCV002314972
NM_005359.6(SMAD4):c.566G>A (p.Arg189His)	SNV Germline	Chr18:51054892	Conflicting classifications of pathogenicity	Hereditary cancer-predisposing syndrome Myhre syndrome Generalized juvenile polyposis/juvenile polyposis coli Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Carcinoma of pancreas Condition: not provided not specified Juvenile polyposis syndrome Hereditary cancer-predisposing syndrome Familial thoracic aortic aneurysm and aortic dissection Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome	Criteria Provided Conflicting Classifications	CA8965830	rs_759288477	8 SubmittersRCV000579689 RCV000764162 RCV001584257 RCV002268143 RCV002231713 RCV002319530 RCV003999046
NM_005359.6(SMAD4):c.1219G>C (p.Val407Leu)	SNV Germline	Chr18:51067098	Conflicting classifications of pathogenicity	Juvenile polyposis syndrome Hereditary cancer-predisposing syndrome Myhre syndrome Generalized juvenile polyposis/juvenile polyposis coli Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Carcinoma of pancreas Condition: not provided Hereditary cancer-predisposing syndrome Familial thoracic aortic aneurysm and aortic dissection Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome	Criteria Provided Conflicting Classifications	CA8966026	rs_147621330	10 SubmittersRCV000558005 RCV000562603 RCV000764164 RCV001662542 RCV002311850 RCV003476248
NM_005359.6(SMAD4):c.298A>C (p.Arg100=)	SNV Germline	Chr18:51048734	Conflicting classifications of pathogenicity	Hereditary cancer-predisposing syndrome Generalized juvenile polyposis/juvenile polyposis coli Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Juvenile polyposis syndrome Familial thoracic aortic aneurysm and aortic dissection Hereditary cancer-predisposing syndrome Myhre syndrome	Criteria Provided Conflicting Classifications	CA8965766	rs_751154230	5 SubmittersRCV000568563 RCV001126988 RCV001126989 RCV001479449 RCV002311908 RCV001126990
NM_005359.6(SMAD4):c.789C>T (p.Asn263=)	SNV Germline	Chr18:51058341	Conflicting classifications of pathogenicity	Hereditary cancer-predisposing syndrome Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Myhre syndrome Generalized juvenile polyposis/juvenile polyposis coli Familial thoracic aortic aneurysm and aortic dissection Hereditary cancer-predisposing syndrome Juvenile polyposis syndrome	Criteria Provided Conflicting Classifications	CA8965907	rs_763510526	4 SubmittersRCV000571444 RCV001124421 RCV001124422 RCV000635500 RCV002311920 RCV001420983
NM_005359.6(SMAD4):c.1308+2T>C	SNV Germline	Chr18:51067189	Pathogenic	Generalized juvenile polyposis/juvenile polyposis coli Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Myhre syndrome	Criteria Provided Single Submitter		rs_1555686624	1 SubmittersRCV000662091 RCV000662093 RCV000662092
NM_005359.6(SMAD4):c.*1874C>G	SNV Germline	Chr18:51080341	Conflicting classifications of pathogenicity	Generalized juvenile polyposis/juvenile polyposis coli Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Myhre syndrome Condition: not provided	Criteria Provided Conflicting Classifications		rs_761701805	2 SubmittersRCV001122227 RCV001122225 RCV001122226 RCV002511046
NM_005359.6(SMAD4):c.*6522C>T	SNV Germline	Chr18:51084989	Conflicting classifications of pathogenicity	Generalized juvenile polyposis/juvenile polyposis coli Myhre syndrome Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Condition: not provided	Criteria Provided Conflicting Classifications		rs_183472455	2 SubmittersRCV001123051 RCV001123052 RCV001123053 RCV002275295
NM_005359.6(SMAD4):c.1447+15C>A	SNV Germline	Chr18:51076791	Conflicting classifications of pathogenicity	Generalized juvenile polyposis/juvenile polyposis coli Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome Juvenile polyposis syndrome Myhre syndrome	Criteria Provided Conflicting Classifications		rs_1910484768	2 SubmittersRCV001127539 RCV001123415 RCV002558220 RCV001123414