Familial non syndromic congenital heart disease (Version 1.90)

Level 3: Congenital heart disease
Level 2: Cardiovascular disorders

Relevant 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, Congenital heart disease, Syndromic congenital heart disease, Isomerism and laterality disorders
Panel types: Rare Disease 100K
Previous code: 583c128f8f62036f70db8d29

Description

This panel is NO LONGER ACTIVELY MAINTAINED.

Please use with caution, as the gene list has not been recently updated. Reviews added to this panel are no longer a priority for curation and may not be followed up.

Please consider using an NHS Genomic Medicine Service (GMS) panel instead. The full list of GMS panels can be found here: https://nhsgms-panelapp.genomicsengland.co.uk/panels, with links back to PanelApp should you wish to leave a review on the panel.

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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

Panel Activity

16 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
Zornitza Stark (Australian Genomics)

Group: Other
Workplace: Other clinical service
Ivone Leong (Genomics England Curator)

Group: Other
Workplace: Other
Ronnie Wright (North West GLH)

Group: NHS Genomic Medicine Centre
Workplace: NHS diagnostic lab
Dmitrijs Rots (Children's Clinical University Hospital)

Group: Other
Workplace: Research lab
Arina Puzriakova (Genomics England Curator)

Group: Other
Workplace: Other

60 Entities

60 reviewed, 33 green

List	Entity	Reviews	Mode of inheritance	Details
Filter Entities 60 Entitiess
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 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 List (high evidence)	ADAMTS19	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Non-syndromic heart valve disease heart valve disease, MONDO:0002869 Tags
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 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 List (high evidence)	CTNND1	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Literature Phenotypes cardiovascular anomalies Tags
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 List (high evidence)	FLNA	2 reviews	X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)	Sources Expert Review Green Literature Radboud University Medical Center, Nijmegen UKGTN Phenotypes Cardiac valvular dysplasia, X-linked, OMIM:314400 Tags
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 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 List (high evidence)	GDF1	5 reviews 1 red	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Congenital heart defects, multiple types, 6, OMIM:613854 Right atrial isomerism (Ivemark), OMIM:208530 Tetralogy of Fallot Double-outlet right ventricle Right atrial isomerism Visceral Heterotaxy, Transposition Of The Great Arteries Tags
Green List (high evidence)	HYAL2	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Muggenthaler-Chowdhury-Chioza syndrome, OMIM:621063 Tags
Green List (high evidence)	7q11.23 recurrent (Williams-Beuren syndrome) region (includes ELN) Loss ISCA-37392-Loss Region	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ClinGen Expert Review Green Phenotypes 194050 Williams syndrome Tags
Green List (high evidence)	22q11.21 recurrent (Cat eye syndrome) region (includes CECR2) Gain ISCA-37393-Gain Region	1 review	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 List (high evidence)	8p23.1 recurrent region (includes GATA4) Gain ISCA-37423-Gain Region	1 review 1 green	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 List (high evidence)	8p23.1 recurrent region (includes GATA4) Loss ISCA-37423-Loss Region	1 review 1 green	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 List (high evidence)	1p36 terminal region (includes GABRD) Loss ISCA-37434-Loss Region	1 review	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 List (high evidence)	22q11.2 recurrent (DGS/VCFS) region (proximal, A-D) (includes TBX1) Loss ISCA-37446-Loss Region	1 review	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 List (high evidence)	17q23.1q23.2 recurrent region (includes TBX2, TBX4) Loss ISCA-37501-Loss Region	2 reviews 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 List (high evidence)	JAG1	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Alagille syndrome 1, OMIM:118450 Tetralogy of Fallot, OMIM:187500 Deafness, congenital heart defects, and posterior embryotoxon, OMIM:617992 Tags
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 List (high evidence)	MYH6	4 reviews	BOTH monoallelic and 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 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 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 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 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 List (high evidence)	SPRED2	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes developmental delay intellectual disability cardiac defects short stature skeletal anomalies a typical facial gestalt Tags
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 List (high evidence)	TBX20	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Atrial septal defect 4, OMIM:611363 atrial septal defect 4, MONDO:0012654 Dilated cardiomyopathy, MONDO:0005021 Tags
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 List (high evidence)	TLL1	3 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Radboud University Medical Center, Nijmegen Phenotypes Atrial septal defect 6, OMIM:613087 Tags
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 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 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 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 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 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 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 List (moderate evidence)	SHROOM3	1 review	Unknown	Sources Expert Review Amber Radboud University Medical Center, Nijmegen Phenotypes Heterotaxy Tags watchlist
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 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 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 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 List (low evidence)	FLT4	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Literature Phenotypes Tetralogy of Fallot Tags
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 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 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, OMIM:241550 Atrioventricular septal defect 3, OMIM:600309 Tags
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 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 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 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 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 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 List (low evidence)	PLXND1	1 review 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Red Literature Phenotypes Truncus arteriosus Tags
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 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 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 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 List (low evidence)	ZFPM2	3 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Tetralogy of Fallot, OMIM:187500 Tags
No list	22q11.2 recurrent (DGS/VCFS) region (proximal, A-B) (includes TBX1) Loss ISCA-37433-Loss Region	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ClinGen Expert Review Removed 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 curated_removed

Familial non syndromic congenital heart disease (Version 1.90)

16 reviewers

60 Entities

60 reviewed, 33 green

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