Table 1:

Current Recommendations and Clinical Utility of Commercially-Available Genetic Tests for Commonly Encountered Heritable Aortopathies and Cardiomyopathies

Class	Disorder	Genes	Clinical Impact	Society Recommendationsb	Ref.
Aortopathies (systemic)	vEDS	COL3A1c	Diagnosis	ACC/AHA/AATS and ESC guidelines: 1) Patients with suspected vEDS based on clinical criteria should be referred to a geneticist to facilitate diagnostic genetic testing for COL3A1 mutations (class I). 2) Mutation-specific cascade screening recommended if a bona fide disease-causative mutation identified (class I).	20, 21
	LDS	TGFBRIc, TGFBR2c, SMAD3, TGFB2, and TGFB3	Diagnosis	ACC/AHA/AATS and ESC guidelines: 1) Patients with suspected LDS based on clinical criteria should be referred to a geneticist to facilitate diagnostic genetic testing (class I). 2) Mutation-specific cascade screening recommended if a bona fide disease-causative mutation identified (class I).	20, 21
	MFS	FBNlc	Diagnosis Risk-stratification Management	ACC/AHA/AATS and ESC guidelines: 1) Patients with suspected MFS based on revised Ghent nosology should be referred to a geneticist to facilitate diagnostic genetic testing (class I). 2) Mutation-specific cascade screening recommended if a bona fide disease-causative mutation identified (class I).	20, 21
Aortopathies (non-systemic)	FTAAD	ACTA2, MAT2A, MYH11, MYLK, PRKG1, and TGFB2	Diagnosis	ACC/AHA/AATS and ESC guidelines:break 1) Known syndromic FTAADs (vascular EDS, LDS, and MFS) should be ruled out and the index case referred to a geneticist for consideration of diagnostic genetic testing (class I). 2) Mutation-specific cascade screening recommended if a bona fide disease-causative mutation identified (class I).	20, 21
Cardiomyopathies	ACM	Major: DSC2c, DSG2c, DSPc, and PKP2c Minor: JUP, RYR2, TGFB3, and TMEM43	Diagnosis Risk-stratification	HRS/EHRA guidelines: 1) Genetic testing can be useful in patients who satisfy 2010 ESC task force diagnostic criteria (class IIa). 2) Mutation-specific cascade screening recommended (class I). 3) Genetic testing can be considered in patients with possible ACM based on 2010 ESC task force diagnostic criteria (class IIb).d	6, 22
	DCM	Autosomal DCM:~60+ genes identified to date. DCM with conduction disease: LMNAc and SCN5A X-linked DCM: DMD and TAZ	Diagnosis Management	HRS/EHRA guidelines: 1)Comprehensive or LMNA/SCN5A targeted genetic testing is recommended for all patients with DCM and significant cardiac conduction disease or family history of SCD (class I) 2) Mutation-specific cascade screening recommended (class I). 3) Comprehensive genetic testing can be useful in confirming the diagnosis of familial DCM and establishing a molecular target for cascade screening (class IIa).d	6
	HCMe	Major: MYBPC3c and MYH7c Minor: ACTC, ACTN2, ANKRD1, CSRP3, JPH2, LBD3, MYH6, MYL2, MYL3, MYOZ2, PLN, TNNC1, TNNI3, TNNT2c, TPM1, TTN, TCAP, and VCL	Diagnosis Risk-stratification Management	ACC/AHA. HRS/EHRA. and ESC guidelines: 1) Genetic testing recommended in patients fulfilling diagnostic criteria for or with signs/symptoms suggestive of HCM (class I). 2) Mutation-specific cascade screening recommended (class I). 3) Genetic testing should be considered in borderline cases after assessment by HCM specialist (class IIa).d 4) Genetic testing should be considered in deceased patients with pathologically confirmed HCM to facilitate cascade screening (class IIa).	6,23,24

^aAATS = American Academy of Thoracic Surgery; ACC = American College of Cardiology; AHA = American Heart Association; ACM, arrhythmogenic cardiomyopathy; DCM = dilated cardiomyopathy; EHRA = European Heart Rhythm Association; ESC = European Society of Cardiology; FTAAD = familial thoracic aortic aneurysm and dissection; HCM = hypertrophic cardiomyopathy; LDS = Loeys-Dietz syndrome; MFS = Marfan syndrome; and vEDS = vascular Ehlers-Danlos syndrome.

^bClass of evidence indicated when available.

^cDenotes commonly encountered genes with strong evidence that disease-causative mutations within these genes contribute directly to disease pathogenesis.

^dUse of large gene panels in weak/borderline clinical cases substantially increases the risk of encountering a non-diagnostic VUS.

^eDenotes the most clinically useful monogenic cardiovascular genetic tests.