Table 1 De novo coding variants in known disease-risk genes

Fam451

LVNC

Triangular face; astigmatism; downslanted palpebral fissures; intellectual disability; small for gestational age; bicuspid aortic valve; inability to walk; proportionate short stature; abnormal vena cava morphology; proportionate shortening of all digits; feeding difficulties in infant; short proximal phalanx of thumb; low hanging columella; broad hallux; keloids; and delayed fine motor development

chr16:89,280,358 GC > G

ANKRD11

Frameshift

c.6183del

p.Leu2062TrpfsTer25

–

–

Fam010

HCM

Depressivity; lethargy; palpitations; and pedal oedema

chr2:219,425,734 C > T

DES

Missense

c.1360C > T

p.Arg454Trp

rs267607490

P/LP

Fam208

DCM

Flexion contracture; congestive heart failure; Achilles tendon contracture; restrictive deficit on pulmonary function testing; skeletal muscle atrophy; progressive muscle weakness; limb muscle weakness; scapular winging; myofibrillar myopathy; skeletal myopathy; knee flexion contracture; limb–girdle muscular dystrophy; and distal lower limb amyotrophy

chr1:156,134,479 T > C

LMNA

Missense

c.590 T > C

p.Leu197Pro

–

–

Fam520

HCM

Hypothyroidism; congestive heart failure; palpitations; and dyspnoea

chr22:20,987,543 C > A

LZTR1

Missense

c.360C > A

p.His120Gln

rs1249605552

US

Fam491

HCM

Congestive heart failure; sudden cardiac death; dyspnoea; and arrhythmia

chr14:23,425,285 C > G

MYH7

Missense

c.2420G > C

p.Arg807Pro

rs141414377

LP

Fam798

HCM

Restrictive cardiomyopathy

chr14:23,429,004 C > T

MYH7

Missense

c.1358G > A

p.Arg453His

rs397516101

P

Fam268

HCM

Angina pectoris; palpitations

chr14:23,425,970 C > T

MYH7

Missense

c.2156G > A

p.Arg719Gln

rs121913641

P

Fam659

LVNC

Atrial septal defect; atrioventricular block; asthma; and abnormal ventricular septum morphology

chr5:173,232,976 G > T

NKX2-5

Missense

c.568C > A

p.Arg190Ser

rs104893906

–

Fam828

HCM

Intellectual disability; failure to thrive; right ventricular cardiomyopathy; and left ventricular non-compaction cardiomyopathy

chr12:112,473,023 A > G

PTPN11

Missense

c.836A > G

p.Tyr279Cys

rs121918456

P/LP

Fam478

HCM

Palpitations

chr3:12,604,188 G > A

RAF1

Missense

c.782C > T

p.Pro261Leu

rs397516828

P

Fam794

ARVC

Cardiac arrest; palpitations

chr1:237,756,289 A > G

RYR2

Missense, splice region

c.11147A > G

p.Glu3716Gly

–

–

Fam231

HCM

Syncope; restrictive cardiomyopathy

chr1:201,365,291 C > T

TNNT2

Missense

c.311G > A

p.Arg104His

rs397516457

P

Fam112

DCM

–

chr2:178,741,570 C > T

TTN

Missense

c.11663G > A

p.Gly3888Glu

–

–