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Table 3 Damaging mosaics in CHD-relevant genes

From: EM-mosaic detects mosaic point mutations that contribute to congenital heart disease

IDGeneVariant classBlood VAFpLIEpiscoreHeartExpAge (year)Clinical phenotypePCGC de novo LoF/Dmis variants in mosaic gene
Cardiac abnormalitiesExtracardiac abnormalities
1-00761FBN1Dmis0.241.0098931–5Mitral stenosisDysmorphic features, subglottic stenosis, hypoplasic left mainstem bronchus, short stature3
1-07004TET3Dmis0.161.007875–18Subaortic stenosisNone0
1-05662SETD2LoF0.131.009985< 1Aortic coarctation, mitral valve hypoplasiaNone0
1-00344UBR5splice0.271.0095905–18D-transposition of the great arteries, VSD, valvar and subvalvar pulmonary stenosisNone0
1-03512RFX3LoF0.091.0010046< 1Tetralogy of Fallot with pulmonary stenosisNone0
1-06216ITSN1Dmis0.211.009886< 1ASDPlagiocephaly, rib anomaly, single kidney, dysmorphic facial features0
1-00363QSER1Dmis0.061.0094791–5Tetralogy of Fallot with pulmonary stenosis, VSDinguinal hernia0
1-13185PKD1Dmis0.101.008784< 1VSD, partially anomalous pulmonary venous returnHemangioma1
1-00192GLYR1Dmis0.220.998993< 1ASD, VSD, interrupted aortic arch, hypoplastic tricuspid valve, BAVNone0
1-04046FZD5Dmis0.090.998948< 1Tetralogy of Fallot with pulmonary stenosis, VSDNone0
1-06649NOVA2Dmis0.150.957556< 1Tetralogy of Fallot with pulmonary stenosisNone0
1-05095ISL1LoF0.070.9097251–5ASDNone0
1-06677KCTD10Dmis0.160.8475915–18Aortic coarctation, pulmonary valve stenosisDysmorphic facial features, hydrocephalus, pyloric stenosis, single kidney, imperforate/atretic anus0
1-05447HNRNPABDmis0.090.7672995–18ASD, BAV, aortic coarctationNone0
1-00021QKILoF0.130.769497< 1Doublet outlet right ventricle, pulmonary stenosis, VSDNone0
1-11871FHOD3Dmis0.180.059192< 1Tetralogy of Fallot with pulmonary atresiaHypocalcemia, thrombocytopenia, lymphopenia0
1-01458HK2Dmis0.270.048990< 1Hypoplastic left heart with aortic and mitral atresia, aortic coarctationNone1
1-00669PRKD3splice0.190.027782< 1D-transposition of the great arteries, conal VSD, bilateral conus, interrupted aortic archNone0
1-00524RNF20LoF0.100.00558318–25Left-dominant complete atrioventricular canalHeterotaxy with situs inversus totalis, asplenia, duodenal atresia0
1-01851SUCLA2LoF0.110.0072895–18Balanced complete atrioventricular canal, aortic coarctationNone0
1-03885LZTR1Dmis0.200.0031845–18Abnormal pulmonary vein draining into the right atriumLeft-sided/midline liver, asplenia, maltrotation2
1-05011KCTD20Dmis0.260.00767718–25Transposition of the great arteries, tricuspid and pulmonary valve atresiaLeft-sided/midline liver1
1-00018Figure 4Dmis0.190.0049705–18BAV, mitral atresia, aortic coarctation, VSD, total anomalous pulmonary venous returnNephritis1
1-05661SMAD9Dmis0.060.0084395–18Common atrioventricular canalNone0
1-09869PIK3C2GLoF0.07*0.0073285–18Common atrioventricular canal, aortic stenosis, aortic arch hypoplasia, VSDsDysmorphic facial features, low-set ears, campomelic dysplasia1
  1. There were 25 potentially pathogenic mosaic mutations based on known gene function and patient phenotype. Some of these probands have previously described rare LoF/Dmis variants, though none are likely pathogenic for CHD {Jin 2017}. Additionally, some genes were previously found to have LoF/Dmis variants among other individuals in this CHD cohort. Age ranges “A-B” denote A < =age < B. Abbreviations: ASD atrial septal defect, BAV bicuspid aortic valve, Dmis deleterious missense, episcore haploinsufficiency score (percentile rank) [29], Heart Exp heart expression percentile rank, LoF loss of function, pLI probability of loss-of-function intolerance, PCGC Pediatric Cardiac Genomics Consortium, VAF variant allele fraction, VSD ventricular septal defect. *VAF refers to CHD tissue WES