Familial pulmonary fibrosis (Version 1.31)

Description

Familial pulmonary fibrosis inclusion criteria

• Clinical syndrome consistent with interstitial lung disease: Breathlessness on exertion or cough, bilateral crepitations on examination,
AND
• A High Resolution CT Scan with evidence of interstitial lung disease, AND
• A first degree relative with an interstitial lung disease

Familial pulmonary fibrosis exclusion criteria
• A respiratory disease other than an interstitial lung disease
• Any cystic lung disease

Prior genetic testing guidance
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition.
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Familial pulmonary fibrosis prior genetic testing genes
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice:
SFTPB, SFTPC in childhood onset cases

Closing statement
These requirements will be kept under continual review during the main programme and may be subject to change.

Panel Activity

12 reviewers

Ellen McDonagh (Genomics England Curator)

Group: Other
Workplace: Other
Helen Savage (Congenica Ltd)

Group: Other biotech or pharmaceutical
Workplace: Other clinical service
Sarah Leigh (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
Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)

Group: NHS Genomic Medicine Centre
Workplace: NHS diagnostic lab
Philip Molyneaux (Imperial College)

Group: Other
Workplace: NHS clinical service
Øystein Holla (Telemark Hospital Trust)

Group: Other
Workplace: Other diagnostic lab
Zornitza Stark (Australian Genomics)

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

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

Group: Other
Workplace: Other

75 Entities

75 reviewed, 26 green

List	Entity	Reviews	Mode of inheritance	Details
Filter Entities 75 Entitiess
Green Green List (high evidence)	ABCA3	4 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Surfactant metabolism dysfunction, pulmonary, 3, 610921 Tags non-coding-known-pathogenic
Green Green List (high evidence)	ACD	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Phenotypes ?Dyskeratosis congenita, autosomal dominant 6, OMIM:616553 ?Dyskeratosis congenita, autosomal recessive 7, OMIM:616553 Tags watchlist_moi
Green Green List (high evidence)	AP3B1	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Pulmonary Fibrosis and Hermansky-Pudlak Syndrome Hermansky-Pudlak syndrome 2, 608233 Pulmonary Disease Pulmonary fibrosis Tags
Green Green List (high evidence)	ASAH1	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Farber lipogranulomatosis, 228000 Tags
Green Green List (high evidence)	CSF2RA	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Surfactant metabolism dysfunction, pulmonary, 4, 300770 Pulmonary alveolar proteinosis Tags Pseudoautosomal region 1
Green Green List (high evidence)	CSF2RB	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Surfactant metabolism dysfunction, pulmonary, 5, 614370 Pulmonary alveolar proteinosis Tags
Green Green List (high evidence)	DKC1	3 reviews 2 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Emory Genetics Laboratory Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Dyskeratosis congenita, X-linked, 305000 Dyskeratosis congenita associated with pulmonary fibrosis Tags
Green Green List (high evidence)	FAM111B	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Literature Phenotypes Poikiloderma, hereditary fibrosing, with tendon contractures, myopathy, and pulmonary fibrosis 615704 Tags
Green Green List (high evidence)	FARSA	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes ?Rajab interstitial lung disease with brain calcifications 2, OMIM:619013 Tags
Green Green List (high evidence)	FARSB	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Rajab interstitial lung disease with brain calcifications, 613658 Tags
Green Green List (high evidence)	GBA	4 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Radboud University Medical Center, Nijmegen UKGTN Phenotypes Gaucher disease, type I, 230800 Gaucher disease with associated Pulmonary Fibrosis Tags new-gene-name
Green Green List (high evidence)	HPS1	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Hermansky-Pudlak syndrome 1, 203300 Pulmonary Fibrosis and Hermansky-Pudlak Syndrome Pulmonary Disease Hermansky-Pudlak Syndrome type 1 associated with pulmonary fibrosis Tags
Green Green List (high evidence)	HPS4	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Hermansky-Pudlak syndrome, 4, 614073 Pulmonary Fibrosis and Hermansky-Pudlak Syndrome Pulmonary Disease Hermansky-Pudlak Syndrome type 4, associated with pulmonary fibrosis Tags
Green Green List (high evidence)	ITGA3	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Radboud University Medical Center, Nijmegen UKGTN Phenotypes Interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa, congenital, 614748 Tags
Green Green List (high evidence)	NKX2-1	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Choreoathetosis, hypothyroidism, and neonatal respiratory distress, 610978 Associated with pulmonary fibrosis, but strong recurrent infection signal Tags
Green Green List (high evidence)	PARN	4 reviews 3 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Eligibility statement prior genetic testing Expert Review Green Phenotypes Pulmonary fibrosis and/or bone marrow failure, telomere-related, 4, OMIM:616371 Tags
Green Green List (high evidence)	RTEL1	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Eligibility statement prior genetic testing Expert Review Green Phenotypes Pulmonary fibrosis and/or bone marrow failure, telomere-related, 3, 616373 Tags
Green Green List (high evidence)	SFTPA2	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Pulmonary fibrosis, idiopathic, 178500 Tags
Green Green List (high evidence)	SFTPB	4 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Eligibility statement prior genetic testing Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Surfactant metabolism dysfunction, pulmonary, 1, 265120 Tags
Green Green List (high evidence)	SFTPC	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Eligibility statement prior genetic testing Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Surfactant metabolism dysfunction, pulmonary, 2, 610913 Interstitial Lung Disease Pulmonary alveolar proteinosis Tags
Green Green List (high evidence)	SLC34A2	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Radboud University Medical Center, Nijmegen Phenotypes Pulmonary alveolar microlithiasis, 265100 Tags
Green Green List (high evidence)	SLC7A7	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Lysinuric protein intolerance, 222700 Tags
Green Green List (high evidence)	SMPD1	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Niemann-Pick disease, type A 257200 Niemann-Pick disease, type B 607616 Tags
Green Green List (high evidence)	TERC	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Eligibility statement prior genetic testing Expert Review Green Phenotypes {Pulmonary fibrosis, idiopathic, susceptibility to}, 614743 Tags locus-type-rna-misc
Green Green List (high evidence)	TERT	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Eligibility statement prior genetic testing Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, OMIM:614742 Tags
Green Green List (high evidence)	TINF2	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Literature Radboud University Medical Center, Nijmegen Phenotypes Dyskeratosis congenita, autosomal dominant, 3, 613990 Associated with dyskeratosis congenita and Fibrosis Tags
Amber Amber List (moderate evidence)	CASR	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Amber Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Hypocalciuric hypercalcemia, type I, 145980 Tags
Amber Amber List (moderate evidence)	ZCCHC8	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Amber Literature Phenotypes ?Pulmonary fibrosis and/or bone marrow failure, telomere-related, 5, OMIM:618674 Tags watchlist
Red Red List (low evidence)	ACVRL1	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Telangiectasia, hereditary hemorrhagic, type 2 Tags
Red Red List (low evidence)	ASCL1	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Central hypoventilation syndrome, congenital Tags
Red Red List (low evidence)	BDNF	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Central hypoventilation syndrome, congenital Tags
Red Red List (low evidence)	BLOC1S3	2 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Hermansky-Pudlak syndrome 8, 614077 Tags
Red Red List (low evidence)	BLOC1S6	2 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Hermansky-pudlak syndrome 9, 614171 Tags
Red Red List (low evidence)	BMPR2	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary hypertension, familial primary, 1, with or without HHT Pulmonary hypertension, primary, fenfluramine or dexfenfluramine-associated Pulmonary venoocclusive disease 1 Tags
Red Red List (low evidence)	CCDC39	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Ciliary dyskinesia, primary, 14 Tags
Red Red List (low evidence)	CCDC40	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Ciliary dyskinesia, primary, 15 Tags
Red Red List (low evidence)	CFTR	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Cystic fibrosis Tags
Red Red List (low evidence)	DNAAF1	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	DNAAF2	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	DNAH11	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	DNAH5	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	DNAI1	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	DNAI2	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	DNAL1	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	DOCK8	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	DTNBP1	2 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Hermansky-Pudlak syndrome 7 614076 Tags
Red Red List (low evidence)	EDN3	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	EFEMP2	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	ELMOD2	2 reviews	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Fibrosis and Hermansky-Pudlak Syndrome Pulmonary Disease Tags
Red Red List (low evidence)	ELN	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	ENG	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	FBLN5	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	FLCN	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	GDNF	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	HPS3	2 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Hermansky-Pudlak syndrome 3 614072 Tags founder-effect
Red Red List (low evidence)	HPS5	2 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Hermansky-Pudlak syndrome 5 614074 Tags
Red Red List (low evidence)	HPS6	2 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Hermansky-Pudlak syndrome 6 614075 Tags
Red Red List (low evidence)	LTBP4	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	MUC5B	2 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Eligibility statement prior genetic testing Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes {Pulmonary fibrosis, idiopathic, susceptibility to}, 178500 Tags promoter
Red Red List (low evidence)	NF1	4 reviews 1 green 2 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Red Literature Phenotypes Neurofibromatosis, type 1 162200 Tags
Red Red List (low evidence)	NME8	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	PHOX2B	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	RET	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	RSPH4A	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	RSPH9	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	SCNN1A	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	SCNN1B	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	SCNN1G	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	SERPINA1	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	SFTPA1	5 reviews 1 green 2 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes {Pulmonary fibrosis, idiopathic, susceptibility to}, 178500 familial idiopathic pulmonary fibrosis Tags
Red Red List (low evidence)	SFTPD	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Tags
Red Red List (low evidence)	SMAD9	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	STAT3	2 reviews 1 red	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Pulmonary Disease Tags
Red Red List (low evidence)	TSC1	4 reviews 2 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Tuberous sclerosis-1 191100 Tags
Red Red List (low evidence)	TSC2	4 reviews 2 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Tuberous sclerosis-2 613254 Tags

Major version comments

Panel reviews were assessed, and panel was revised according to reviews and further curation. 27th April 2017

Familial pulmonary fibrosis (Version 1.31)

12 reviewers

75 Entities

75 reviewed, 26 green

4 reviews

Sources

Phenotypes

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3 reviews

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Phenotypes

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2 reviews

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1 review

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3 reviews

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3 reviews

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3 reviews

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1 review

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2 reviews

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1 review

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4 reviews

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3 reviews

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2 reviews

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1 review

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3 reviews

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4 reviews

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2 reviews

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2 reviews

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4 reviews

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