Table 2 Variants of potential clinical relevance.
From: The Cardiac Genome Clinic: implementing genome sequencing in pediatric heart disease
ID | Cardiac lesion | Other anomalies | Gene(s) | Variant | Inheritance | Variant interpretation | Clinical assessment | Diagnosis |
|---|---|---|---|---|---|---|---|---|
042 | AVSD | Feeding difficulties, polyhydramnios, deceased at 7 months | ANKRD11 (NM_013275.5) | c.5238_5239delGC, p.(Pro1747Argfs*49) | De novo | Pathogenic | Causative (CHD, other anomalies)b | KBG syndrome |
087 | Dextrocardia, left atrial isomerism, AVSD, hypoplastic LV, DORV | Macrocephaly, left-sided liver, polysplenia, right-sided stomach, ultrastructural ciliary abnormalities | DNAH9 (NM_001372.3) | c.[4421A>G];[13244T>C], p.[(Asp1474Gly)];[(Ile4415Thr)] | Paternal; maternal | Uncertain significance | Causative (CHD, other anomalies)b | Primary ciliary dyskinesia |
034 | TOF, PA, MAPCAS | - (Mild congenital lymphedema) | FLT4a (NM_182925.4) | c.89delC, p.(Pro30Argfs*3) | Maternal | Likely pathogenic | Causative (CHD)b | Nonsyndromic TOF |
148 | AS, CoA, VSD | Developmental delay, failure to thrive, dysmorphisms | KMT2D (NM_003482.3) | c.15673C>T, p.(Arg5225Cys) | De novo | Likely pathogenic | Causative (CHD, other anomalies)b | Kabuki syndrome |
054 | PDA | - | MYH11 (NM_002474.2) | c.4578+1G>A, p.? | Paternal | Pathogenic | Causative (CHD)b | Familial PDA |
027 | AS | Developmental delay, microcephaly, short stature, hypotonia | NEXMIF (NM_001008537.2) | c.1502delG, p.(Gly501Valfs*4), hemizygous | Maternal (X-linked) | Likely pathogenic | Causative (CHD, other anomalies)b | NEXMIF-related developmental disorder |
032 | AVSD, hypoplastic right ventricle | Developmental delay, borderline microcephaly, hypotonia | NIPBL (NM_133433.3) | c.771+1G>A, p.? | Maternal | Pathogenic | Causative (CHD, other anomalies)b | Cornelia de Lange syndrome |
033 | TOF, PA | - | NOTCH1 deletion (i) | 9q34.3 deletion (138 kb) | Unknown | Pathogenic | Causative (CHD)b | NOTCH1-related CHD |
039 | CoA, BAV, muscular VSD | Intellectual disability, macrocephaly, hemangioma, scoliosis | NR2F2 (NM_021005.3) | c.671T>A, p.(Val224Asp) | De novo | Likely pathogenic | Causative (CHD), possibly causative (other anomalies)b | NR2F2-related CHD |
157 | HLHS (mitral atresia, aortic atresia) | Developmental delay, borderline short stature, hypotonia | POGZ (NM_015100.3) | c.3403delG, p.(Glu1135Argfs*3) | De novo | Pathogenic | Causative (CHD, other anomalies)b | White–Sutton syndrome |
018 | PS | Borderline short stature | PTPN11 (NM_002834.4) | c.209A>G, p.(Lys70Arg) | Maternal | Likely pathogenic | Causative (CHD, other anomalies)b | Noonan syndrome |
060 | CoA, VSD | Increased nuchal translucency, failure to thrive, short stature, dysmorphisms, hypotonia | PTPN11 (NM_002834.4) | c.923A>G, p.(Asn308Ser) | De novo | Pathogenic | Causative (CHD, other anomalies)b | Noonan syndrome |
013 | VSD | Developmental delay, infantile spasms, hypoventilation, macrosomia, macrocephaly, hypotonia | PTEN (NM_000314.4) | c.395G>A, p.(Gly132Asp) | De novo | Pathogenic | Causative (other anomalies) | PTEN hamartoma syndrome |
PURA (NM_005859.4) | c.812_814delTCT, p.(Phe271del) | De novo | Pathogenic | Causative (CHD, other anomalies)b | PURA-related developmental disorder | |||
074 | Interrupted aortic arch type B, large VSD | Borderline short stature, hearing impairment, dysplastic ears with preauricular tags | SALL1 deletion (ii) | 16q12.1-16q12.2 (4.1 Mb) | De novo | Pathogenic | Causative (CHD, other anomalies)b | Townes–Brocks syndrome |
010 | Hypertrophic cardiomyopathy | FLNC (NM_001458.4) | c.6238G>C, p.(Gly2080Arg) | Paternal | Uncertain significance | Likely causative | Hypertrophic cardiomyopathy | |
093 | Dextrocardia, right atrial isomerism, AVSD, PA | Failure to thrive, short stature, borderline microcephaly, asplenia, right-sided stomach | DNAH8 (NM_001206927.1) | c.[991A>G];[10773C>G], p.[(Thr331Ala)];[(Phe3591Leu)] | Paternal; maternal | Uncertain significance | Likely causative | Primary ciliary dyskinesia |
(iii) | 3p11.2-3p12.3 deletion (8.3 Mb) | Maternal | Uncertain significance | Uncertain | Unknown | |||
019 | Interrupted aortic arch type B, AS | Apnea, microcephaly, dysmorphisms, anemia, hyponatremia, deceased at 2 months | (iv) | 15q13.2-15q13.3 duplication (2.4 Mb) | Paternal | Uncertain significance | Uncertain | Unknown |
024 | Transposition of the great arteries | Mild intellectual disability, autism | (v) | 16p13.3 duplication (697 kb) | Maternal | Uncertain significance | Uncertain | Unknown |
099 | Tricuspid valve dysplasia, hypoplastic right heart, VSD, ASD | Mild intellectual disability, ADHD, periauricular skin tag | (vi) | 3p26.1-3pter deletion (4.3 Mb), 3p26.1 duplication (1.8 Mb) | Maternal | Uncertain significance | Uncertain | Unknown |
149 | CoA, BAV | (vii) | 2p13.1-2p12 deletion (594 kb) | Paternal | Uncertain significance | Uncertain | Unknown | |
044 | CoA, multiple VSD | Mild developmental delay, borderline macrocephaly | PTEN (NM_000314.6) | c.45A>C, p.(Arg15Ser) | Paternal | Pathogenic | Causative (other anomalies) | PTEN hamartoma syndrome |
059 | Large ASD secundum | DSG2 deletion (viii) | 18q12.1 (9.1 kb) | De novo | Likely pathogenic | Secondary finding | Arrhythmogenic right ventricular cardiomyopathy |
