Table 2.
De novo coding variants in candidate cardiomyopathy genes
| Family ID | Disease | HPO terms | Genomic position (GRCh38) | Gene | Exomiser rank | Exomiser score | Consequence | cDNA | Variation | rsID |
|---|---|---|---|---|---|---|---|---|---|---|
| Fam003 | HCM | Ptosis; congestive heart failure; delayed gross motor development; and feeding difficulties | chr19:1,061,809 G > T | ABCA7 | – | – | Missense | c.5491G > T | p.Ala1831Ser | – |
| Fam027 | DCM | Failure to thrive | chr4:13,376,561 T > C | RAB28 | – | – | Missense | c.557A > G | p.Glu186Gly | – |
| Fam043 | ARVC | Dilated cardiomyopathy; cardiac arrest; palpitations; abnormal atrioventricular conduction; and arrhythmia | chr19:899,621 G > C | R3HDM4 | – | – | Stop gained | c.627C > G | p.Tyr209Ter | – |
| Fam061 | HCM | Left ventricular dysfunction | chr1:39,297,744 T > TG | MACF1 | – | – | Frameshift, splice region | c.2481 + 1dup | – | – |
| Fam062 | LVNC | Failure to thrive; small for gestational age; ventricular septal defect; restrictive cardiomyopathy; hypertrophic cardiomyopathy; dyspnoea; and right ventricular cardiomyopathy | chr12:49,128,718 T > C | TUBA1B | 1 | 0.7430 | Missense | c.596A > G | p.Asp199Gly | – |
| Fam137b | DCM | Congestive heart failure; dyspnoea; arrhythmia; and bundle branch block | chr14:77,887,137 C > G | ADCK1 | 3 | 0.7504 | Missense | c.470C > G | p.Ala157Gly | – |
| Fam137a | DCM | Hypertension; palpitations | chr4:127,764,330 C > T | SLC25A31 | – | – | Stop gained | c.448C > T | p.Arg150Ter | rs1464153404 |
| Fam190 | HCM | – | chrX:118,608,357 G > C | DOCK11 | 2 | 0.7716 | Splice donor | c.2877 + 1G > C | – | – |
| Fam197 | DCM | Syncope; arrhythmia | chr19:48,627,746 C > T | SPHK2 | 1 | 0.7537 | Missense | c.566C > T | p.Pro189Leu | – |
| Fam225 | DCM | Arrhythmia; dyspnoea; nonorganic psychosis; self-harm; eating disorder; and deceased | chr17:41,909,667 G > A | ACLY | – | – | Stop gained | c.379C > T | p.Arg127Ter | rs1555633336 |
| chr15:55,360,123 T > TTTA | CCPG1 | Inframe insertion | c.1647_1649dup | p.Asn549dup | – | |||||
| Fam231 | HCM | Syncope; restrictive cardiomyopathy; and dyspnoea | chr14:59,263,526 T > C | DAAM1 | 2 | 0.7490 | Missense | c.49 T > C | p.Cys17Arg | – |
| Fam252 | DCM | Failure to thrive; congestive heart failure; and dyspnoea | chr1:110,674,209 C > A | KCNA3 | 1 | 0.7591 | Stop gained | c.601G > T | p.Glu201Ter | – |
| Fam303 | DCM | Eczema; umbilical hernia; and ventricular septal defect | chr1:202,729,832 C > A | KDM5B | 3 | 0.7528 | Stop gained | c.4372G > T | p.Glu1458Ter | – |
| Fam313 | DCM | Café au lait spot; pulmonic stenosis; dyspnoea; tricuspid regurgitation; right ventricular cardiomyopathy; and dysplastic tricuspid valve | chr5:90,642,886 C > T | ADGRV1 | 3 | 0.7832 | Stop gained | c.2398C > T | p.Arg800Ter | rs373780305 |
| Fam373 | HCM | Palpitations; arrhythmia | chrX:136,682,757 C > G | ARHGEF6 | – | – | Splice donor | c.1479 + 1G > C | – | – |
| Fam484 | LVNC | Intellectual disability; joint hypermobility; Wolff–Parkinson–White; and palpitations | chr15:80,173,016 C > T | FAH | – | – | Stop gained, splice region | c.709C > T | p.Arg237Ter | rs769550316 |
| Fam499 | HCM | Multifactorial inheritance; familial predisposition; cardiac arrest; and deceased | chr2:240,462,562 G > A | GPC1 | – | – | Missense | c.697G > A | p.Val233Met | rs748327513 |
| Fam543 | HCM | Angina pectoris; restrictive cardiomyopathy | chr22:18,083,639 C > T | PEX26 | – | – | Stop gained | c.574C > T | p.Arg192Ter | rs61752136 |
| Fam567 | HCM | Thin upper lip vermillion; pointed chin; broad forehead; and long palpebral fissure | chr11:47,245,544 G > C | ACP2 | – | – | Missense | c.479C > G | p.Pro160Arg | – |
| chr21:21,418,570 G > T | NCAM2 | – | – | Splice donor | c.1480 + 1G > T | – | – | |||
| Fam571 | DCM | Failure to thrive; congestive heart failure; and dyspnoea | chr10:133,186,264 C > T | KNDC1 | 2 | 0.7507 | Stop gained | c.916C > T | p.Gln306Ter | – |
| Fam659b | LVNC | Atrial septal defect; atrioventricular block; asthma; and abnormal ventricular septum morphology | chr5:141,398,519 C > G | PCDHGB5 | – | – | Missense | c.392C > G | p.Pro131Arg | rs780671252 |
| Fam728 | LVNC | Aortic valve stenosis; aortic regurgitation; and pulmonary insufficiency | chr2:237,344,691 C > T | COL6A3 | – | – | Missense | c.7327G > A | p.Ala2443Thr | rs1345727801 |
| Fam733 | HCM | – | chr15:22,933,819 G > T | CYFIP1 | 1 | 0.7706 | Stop gained | c.975C > A | p.Tyr325Ter | – |
| Fam806 | LVNC | Primum atrial septal defect | chr19:10,143,859 C > T | DNMT1 | – | – | Missense | c.3023G > A | p.Arg1008Gln | rs746527645 |
| chr16:17,198,230 G > A | XYLT1 | – | – | Missense | c.1271C > T | p.Ala424Val | rs148488379 | |||
| Fam862 | DCM | – | chr8:63,026,259 G > T | GGH | – | – | Missense | c.398C > A | p.Thr133Lys | – |
| Fam906 | HCM | Hypertension | chr6:98,899,282 G > A | FBXL4 | – | – | Stop gained | c.1303C > T | p.Arg435Ter | rs201889294 |
Variants were retained if they had a REVEL score of > 0.5, GERP + + score > 2, CADD score of > 20 and MAF < 0.001, suggesting high pathogenicity. The overall Exomiser score (from 0 to 1) is shown for variants that were ranked in the top three