Description
This panel is a combined panel for the following disorders:
- Fallots tetralogy
- Hypoplastic Left Heart Syndrome
- Left Ventricular Outflow Tract obstruction disorders
- Pulmonary atresia
- Transposition of the great vessels
- Familial non-syndromic congenital heart disease
- Familial congenital heart disease

It was originally developed for the 100,000 Genomes Project and is still being used for participants in the project. For the rare disease eligibility criteria refer to: https://www.genomicsengland.co.uk/rarediseasecriteria100K

12 reviewers

  • Ellen McDonagh (Genomics England Curator)

    Group: other
    Workplace: other

  • Bernard Keavney (The University of Manchester)

    Group: GeCIP domain
    Workplace: Other clinical service

  • Richard Scott (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Sarah Leigh (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Kirsty McCaffrey (Manchester Centre for Genomic Medicine)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS diagnostic lab

  • Rebecca Foulger (Genomics England curator)

    Group: Other
    Workplace: Other

  • Alice Gardham (Genomics England)

    Group: Other
    Workplace: Other

  • Louise Daugherty (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Helen Brittain (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Eleanor Williams (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Rachel Jones (GSTT)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS clinical service

  • Ronnie Wright (North West GLH)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS diagnostic lab

56 Entities

49 reviewed, 28 green

List Entity Reviews Mode of inheritance Details
56 Entitiess
Green Green List (high evidence)
ABL1
2 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Congenital heart defects and skeletal malformations syndrome, 617602
Tags
  • missense
Green Green List (high evidence)
ACVR2B
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Illumina TruGenome Clinical Sequencing Services
  • Literature
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Heterotaxy syndrome
  • Heterotaxy, visceral, 4, autosomal, 613751
  • Visceral Heterotaxy
  • Heterotaxy, Visceral, 4, Autosomal
Tags
Green Green List (high evidence)
CFAP53
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
Phenotypes
  • Visceral Heterotaxy
  • Heterotaxy, Visceral, 6, Autosomal
Tags
Green Green List (high evidence)
CFC1
4 reviews
1 green 1 red
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Heterotaxy, visceral, 2, autosomal, 605376
Tags
Green Green List (high evidence)
ELN
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Supravalvar aortic stenosis, 185500
Tags
Green Green List (high evidence)
FLNA
1 review
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
  • Literature
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Cardiac valvular dysplasia, X-linked 314400
Tags
Green Green List (high evidence)
GATA4
2 reviews
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • ?Testicular anomalies with or without congenital heart disease, 615542
  • Atrial septal defect 2, 607941
  • Atrioventricular septal defect 4, 614430
  • Tetralogy of Fallot, 187500
  • Ventricular septal defect 1, 614429
Tags
Green Green List (high evidence)
GATA6
2 reviews
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Tetralogy of Fallot
Tags
Green Green List (high evidence)
GDF1
4 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Tetralogy of Fallot
  • Double-outlet right ventricle, 217095
  • Right atrial isomerism, 208530
  • Visceral Heterotaxy, Transposition Of The Great Arteries, Dextro-Looped 3
Tags
Green Green List (high evidence)
7q11.23 recurrent (Williams-Beuren syndrome) region (includes ELN) Loss
ISCA-37392-Loss
Region
0 reviews
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • ClinGen
  • Expert Review Green
Phenotypes
  • 194050
  • Williams syndrome
Tags
Green Green List (high evidence)
22q11.21 recurrent (Cat eye syndrome) region (includes CECR2) Gain
ISCA-37393-Gain
Region
0 reviews
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • ClinGen
  • Expert Review Green
Phenotypes
  • PMID 22890013: variable phenotype including developmental delay, ocular coloboma, preauricular tags/pits, cleft palate, skeletal defects, heart defects, urogenital defect, anal defect, hearing loss, clinodactyly of fifth fingers, umbilical hernia, accessory spleen, strabismus, shortening of the fifth finger. PMID 22495764: Inter and intra individual variability of phenotype, mosaic. PMID 11693792: preauricular skin tags and pits, downslanting palpebral fissures, hypertelorism, ectopic anus, hypospadias, and hypoplastic left heart syndrome
  • 115470
Tags
Green Green List (high evidence)
8p23.1 recurrent region (includes GATA4) Gain
ISCA-37423-Gain
Region
0 reviews
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • ClinGen
  • Expert Review Green
Phenotypes
  • Behavioral problems, cleft lip and/or palate, macrocephaly, and seizures were confirmed as additional features among the new patients, and novel features included neonatal respiratory distress, attention deficit hyperactivity disorder (ADHD), ocular anomalies, balance problems, hypotonia, and hydrocele.
  • mild to moderate developmental delay, intellectual disability, mild facial dysmorphism (incl. prominent forehead, arched eyebrows, broad nasal bridge, upturned nares, cleft lip and/or palate) and congenital cardiac anomalies (e.g., atrioventricular septal defect). Other reported features include macrocephaly, behavioral abnormalities (e.g., attention deficit disorder), seizures, hypotonia and ocular and digital anomalies (poly/syndactyly)
  • congenital heart disease
  • 8p23.1 duplication syndrome
Tags
Green Green List (high evidence)
8p23.1 recurrent region (includes GATA4) Loss
ISCA-37423-Loss
Region
0 reviews
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • ClinGen
  • Expert Review Green
Phenotypes
  • prenatal and postnatal growth retardation, low birth weight, mild to moderate intellectual deficit, psychomotor retardation, poor speech, seizures, behavioral problems such as hyperactivity and impulsiveness. Frequent craniofacial abnormalities include microcephaly, high and narrow forehead, broad nasal bridge, epicanthic folds, high arched palate, short neck and low set unusually shaped ears. Furthermore congenital heart defects (atrioventricular, septal defects, pulmonary stenosis), congenital diaphragmatic hernia and in boys cryptorchidism and hypospadias have been frequently reported.
  • congenital heart defects, microcephaly, psychomotor delay and behavioural problems
  • hyperactivity, craniofacial abnormalities
  • 8p23.1 microdeletion syndrome
  • moderate intellectual disability
Tags
Green Green List (high evidence)
22q11.2 recurrent (DGS/VCFS) region (proximal, A-B) (includes TBX1) Loss
ISCA-37433-Loss
Region
0 reviews
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • ClinGen
  • Expert Review Green
Phenotypes
  • 188400
  • immune deficiency
  • renal anomalies
  • 22q11.2 deletion syndrome
  • 192430
  • facial dysmorphic features, high frequency of cardiac defects, including conotruncal defects, prematurity, growth restriction, microcephaly, and mild developmental delay
  • cleft palate, polydactyly
  • polyhydramnios
  • Velocardiofacial syndrome
  • diaphragmatic hernia
  • DiGeorge syndrome
  • congenital heart disease
  • Learning difficulties
Tags
Green Green List (high evidence)
1p36 terminal region (includes GABRD) Loss
ISCA-37434-Loss
Region
0 reviews
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • ClinGen
  • Expert Review Green
Phenotypes
  • posteriorly rotated, low-set, abnormal ears
  • brachycephaly
  • epicanthus
  • heart defects
  • pointed chin
  • deep-set eyes
  • microcephaly
  • hypotonia
  • seizures
  • poor/absent speech
  • central nervous system anomalies
  • large anterior fontanels
  • microbrachycephaly
  • mental retardation
  • growth impairment
  • large, late-closing anterior fontanel
  • flat nose
  • nasal bridge
  • developmental delay
  • hearing impairment
  • distinct dysmorphic features
  • 1p36 deletion syndrome
  • 607872
Tags
Green Green List (high evidence)
22q11.2 recurrent (DGS/VCFS) region (proximal, A-D) (includes TBX1) Loss
ISCA-37446-Loss
Region
0 reviews
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • ClinGen
  • Expert Review Green
Phenotypes
  • 188400
  • neonatal hypocalcemia, which may present as tetany or seizures, due to hypoplasia of the parathyroid glands, and susceptibility to infection due to a deficit of T cells
  • micrognathia
  • clefting
  • Hearing deficits
  • Velocardiofacial syndrome
  • cardiac malformations
  • DiGeorge syndrome
Tags
Green Green List (high evidence)
17q23.1q23.2 recurrent region (includes TBX2, TBX4) Loss
ISCA-37501-Loss
Region
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert list
  • Expert Review Green
Phenotypes
  • Chromosome 17q23.1-q23.2 deletion syndrome, 613355
  • PMID:20206336 mild to moderate developmental delay (particularly speech delay), microcephaly, postnatal growth retardation, heart defects, hand, foot and limb abnormalities
  • PMID: 22052739 Developmental delay, heart defects, microcephaly, postnatal growth retardation, hand, foot and limb abnormalities, sensorineural hearing loss
Tags
Green Green List (high evidence)
JAG1
2 reviews
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Tetralogy of Fallot
  • Alagille syndrome
Tags
Green Green List (high evidence)
MMP21
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Heterotaxy,visceral,7,autosomal, 616749
Tags
Green Green List (high evidence)
MYH6
3 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Literature
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Atrial septal defect 3 614089
  • Shone complex
Tags
Green Green List (high evidence)
NKX2-5
2 reviews
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Mutations in the NKX2-5 gene have been associated with atrioventricular (AV) conduction block, septal defects, conotruncal abnormalities (particularly Tetrology of Fallot), and AV valve formation defects.
  • Hypoplastic left heart syndrome 2
  • Atrioventricular (AV) conduction block
  • septal defects
  • conotruncal abnormalities, particularly Tetrology of Fallot
  • AV valve formation defects
Tags
Green Green List (high evidence)
NODAL
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Literature
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Heterotaxy syndrome
  • Heterotaxy, visceral, 5, 270100
  • Visceral Heterotaxy
  • Heterotaxy, Visceral, 5, Autosomal
Tags
Green Green List (high evidence)
NOTCH2
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Alagille syndrome 2 610205
Tags
Green Green List (high evidence)
NR2F2
2 reviews
1 green 1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Congenital heart defects, multiple types, 4 615779
Tags
Green Green List (high evidence)
TAB2
4 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Literature
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Congenital heart defects, nonsyndromic, 2 614980
Tags
Green Green List (high evidence)
TBX5
2 reviews
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Holt-Oram syndrome, 142900
Tags
Green Green List (high evidence)
TRAF7
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Cardiac, facial, and digital anomalies with developmental delay 618164
Tags
  • missense
Green Green List (high evidence)
ZIC3
1 review
1 green
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Literature
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • x-linked Heterotaxy syndrome, Visceral, 1
  • Heterotaxy, visceral, 1, X-linked 306955
  • Visceral Heterotaxy
  • Heterotaxy, Visceral, 1, X-Linked
Tags
Amber Amber List (moderate evidence)
ACTC1
2 reviews
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Atrial septal defect 5, 612794
Tags
Amber Amber List (moderate evidence)
CRELD1
2 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Atrioventricular septal defect, partial, with heterotaxy syndrome 606217
Tags
  • watchlist
Amber Amber List (moderate evidence)
GATA5
1 review
Not set
Sources
  • Expert Review Amber
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Tetralogy of Fallot (Wei (2013) Int J Med Sci 10,34)
Tags
Amber Amber List (moderate evidence)
LEFTY2
1 review
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Illumina TruGenome Clinical Sequencing Services
  • Literature
Phenotypes
  • Heterotaxy syndrome
Tags
  • watchlist
Amber Amber List (moderate evidence)
NOTCH1
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Sources
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Aortic valve disease 1, 109730
Tags
Amber Amber List (moderate evidence)
SHROOM3
1 review
Unknown
Sources
  • Expert Review Amber
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Heterotaxy
Tags
  • watchlist
Amber Amber List (moderate evidence)
TBX20
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Atrial septal defect 4 611363
Tags
Red Red List (low evidence)
ALDH1A2
1 review
Not set
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Tetralogy of Fallot (Pavan (2009) BMC Med Genet 10, 113)
Tags
Red Red List (low evidence)
CITED2
2 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Literature
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Atrial septal defect, 8 614433, Ventricular septal defect 2, 614431
Tags
Red Red List (low evidence)
CRKL
1 review
Not set
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Tetralogy of Fallot (Tomita-Mitchell (2012) Physiol Genomics 44,518)
Tags
Red Red List (low evidence)
DISP1
1 review
1 red
Not set
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Craniofacial and neuro-developmental abnormalities (Roessler (2009) Hum Genet125,393)
  • Diaphragmatic hernia, congenital (Kantarci (2010) Am J Med Genet A 152A,2493)
  • Tetralogy of Fallot (Silversides (2012) PLoS Genet 8, e1002843)
Tags
Red Red List (low evidence)
FLT4
1 review
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Literature
Phenotypes
  • Tetralogy of Fallot
Tags
Red Red List (low evidence)
FOXH1
1 review
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Literature
Phenotypes
  • Venticular septal defect, transposition of the great arteries
Tags
Red Red List (low evidence)
FOXL1
1 review
1 red
Not set
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Hypoplastic left heart syndrome (Iascone (2012) Clin Genet 81,542)
Tags
Red Red List (low evidence)
GJA1
3 reviews
1 red
Not set
Sources
  • Expert Review Red
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Hypoplastic left heart syndrome 1
  • Hypoplastic Left Heart Syndrome
Tags
Red Red List (low evidence)
HAND2
1 review
1 red
Not set
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Tetralogy of Fallot (Topf (2014) PLoS One 9,e95453)
Tags
Red Red List (low evidence)
IRX4
1 review
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Literature
Phenotypes
  • Ventricular septal defect
Tags
Red Red List (low evidence)
MED13L
3 reviews
1 red
Not set
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Transposition of the great arteries, dextro-looped 1, 608808
Tags
Red Red List (low evidence)
MYOM2
1 review
1 red
Not set
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Tetralogy of Fallot (Grunert (2014) Hum Mol Genet 23,3115)
Tags
Red Red List (low evidence)
NFATC1
1 review
1 red
Not set
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Tetralogy of Fallot (Silversides (2012) PLoS Genet 8)
Tags
Red Red List (low evidence)
NKX2-6
1 review
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • Literature
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Conotruncal heart malformations 217095, Persistent truncus arteriosus 217095
Tags
Red Red List (low evidence)
PLXND1
1 review
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Literature
Phenotypes
  • Truncus arteriosus
Tags
Red Red List (low evidence)
RPSA
1 review
1 red
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Asplenia, isolated congenital, 271400
Tags
Red Red List (low evidence)
SEMA3D
1 review
1 red
Not set
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Tetralogy of Fallot (Siversides (2012) PLoS Genet 8,e1002843)
Tags
Red Red List (low evidence)
SMAD6
1 review
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Literature
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Aortic valve disease 2, 614823
Tags
Red Red List (low evidence)
TBX1
4 reviews
1 red
Not set
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Tetralogy of Fallot
Tags
Red Red List (low evidence)
TLL1
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Literature
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Atrial septal defect 6 613087
Tags
Red Red List (low evidence)
ZFPM2
3 reviews
1 red
Not set
Sources
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Tetralogy of Fallot
Tags

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