Table.

Reasons for Referral to the Yale Program for Cardiovascular Genetics Clinic and the Genes With Variants Identified as VUS or as Pathogenic

Clinical DiagnosisPatients,
n (% of Total)
Pathogenic Mutation Identified,
n (%)
Likely Pathogenic Mutation Identified, n (%)VUS Identified,
n (%)
Candidate Gene Identified, n (%)Genes
Connective tissue disease37 (18.5)3 (8.1)1 (2.7)11 (29.7)7 (18.9)COL1A1, COL5A1,* COL5A2, ELN, FBN1,* FBN2, FLNA,* MYH11, MYLK, PTPN11, SKI, SMAD3, TGFBR2
Sudden cardiac death35 (17.5)8 (22.8)3 (8.5)9 (26.4)6 (17.6)ACTN2, ANK2, AKAP9, CACNA1D,* DPP6, DSG2, DSP,* GYG1, KCNH2,* LMNA, MYBPC3,* MYH6, MYPN, NEXN, PNN, RBM20, RYR2, SCN5A,* TGFB3, TNNI3,* TTN*
HCM28 (14)8 (28.5)5 (17.5)9 (32.1)2 (7.1)ACTN2, AKAP9, ABCC9,* CALR3, JPH2,* MYBPC3,* MYH6, MYH7,* PRKAG2,* TCAP, TTN, TNNT2,* TPM1,* TRPM4*
DCM24 (12)4 (16.6)0 (0)9 (37.5)3 (12.5)BAG3, DSP, DSG2, HFE,* LMNA,* MYBPC3, MYH6, MYH7, PRDM16, PRKAG2, RBM20, SCN5A, TTN*
FH/Lipodystrophy21 (10.5)6 (28.5)2 (9.5)1 (4.7)5 (23.8)APOB,* APOE,* LDLR,* LMNA,* PLAT, PLIN1
LQTS15 (7.5)3 (20)0 (0)3 (20)4 (26.6)AKAP9, ANK2,* CAV3, CTNNA3, KCNQ1,* RBM20, SCN5A, TTN
Atrial or ventricular arrhythmias10 (5.0)0 (0)0 (0)4 (40.0)0 (0)ABCC9, CACNB2, GPD1L, KCNE2, SYNE2
BrS9 (4.5)1 (11.1)2 (22.2)3 (33.3)0 (0)CACNA1C, DSP, RYR2,* SCN5A*
Family history of SCD or LQTS9 (4.5)0 (0)1 (11.1)5 (55.5)1 (11.1)ANK2, CACNA1C, DES,* DSG2, SCN4B, SCN5A, MYH6, TMEM43, TNNI3, VCL
Nonspecific NICM6 (3)2 (33.3)1 (16.6)2 (33.3)0 (0)AKAP9, LAMP2, LDB3, MIB1,* MYH6, NEXN, PKP2,* RYR2, SCN5A, TNNT2, TTN*
Other6 (3)0 (0)2 (33.3)0 (0)1 (20)DSP, EMD,* NDUFV2,* TNNT2*
  • BrS indicates Brugada syndrome; FH, familial hypercholesterolemia; HCM, hypertrophic cardiomyopathy; LQTS, long QT syndrome; NICM, nonischemic cardiomyopathy; SCD, sudden cardiac death; and VUS, variant of uncertain significance.

  • * Indicates gene variants identified as VUS or pathogenic.