In October 2018, the National Test Directory for Rare and Inherited Disease was published. The National Test Directory is updated each year to ensure access to the latest diagnostics and treatments.

The Directory specifies which genomic tests are commissioned by the NHS in England, the technology by which the tests are available, and the patients who will be eligible to access each test.

A document outlining the eligibility criteria for testing supplements the National Genomic Test Directory. It lists the clinical specialties who would be expected to request for a given clinical indication and sets out which patients should be considered for testing under that indication. This will help you to identify the most appropriate test for your patient. This information should be added to your test referral form.

An appropriate discussion of genomic testing and the possible implications for a patient and their family members must take place prior to testing.  A record of this discussion must be retained within the patient record when a genomic test is ordered.

The test directory is updated regularly and we share vital updates and information with clinicians across our region. Recent updates within rare disease are available to view below.

8 April 2026

R code Clinical indication name Summary of changes
R137 Congenital heart disease – microarray Added to eligibility criteria:

Complex congenital heart disease in a neonate/infant undergoing corrective surgery, in whom other syndromic features may not yet be apparent AND a syndromic diagnosis may impact surgical decision making.  Test requests must be approved by clinical genetics to proceed.

Amendments to the criteria already present by stating congenital heart disease refers to complex CHD and cleft palate and / or disorder of calcium homeostasis should be present.

Provided an example of non-syndromic CHD in the exclusion criteria: isolated VSD/ASD
R125 Thoracic aortic aneurysm or dissection Removed criterion points 3. 4. and 7.

Changed threshold for z score in the definition of thoracic aortic aneurysm in children, from >2 to >3.
R132 Dilated and arrhythmogenic cardiomyopathy Corrected an error by removing criterion 1c.
R135 Paediatric or syndromic cardiomyopathy Corrected criterion 2 for clarity.
R140 Elastin-related phenotypes Added to the overlapping clinical indications that patients must meet the criteria for the overlapping clinical indications if these are felt a better test for their patients.
R code Clinical indication name Summary of changes
R441 Unexplained death in infancy and sudden unexplained death in childhood Provided more information in the testing criteria and “where in the pathway” to link with the Joint Agency Response.

Clarification that DNA from both biological parents is preferential and to contact the laboratory if this is not possible.

Exclusion criteria have been added:

Testing should not be performed where the likelihood of a monogenic disorder is low for example where the available evidence supports a non-genetic cause of death (e.g. severe infection, suspicious death/homicide investigation).

Requesting specialties:

Added that these should be in liaison with the designated doctor for child deaths.
R code Clinical indication name Summary of changes
R26 Likely common aneuploidy Removed R297 from the overlapping Clinical Indications as R297 has been retired – see separate entry for R297 for details.
R27 Paediatric disorders Added criteria for unexplained epilepsy as the separate clinical indication for Epilepsy (R59) has been retired.

Added to additional text in the overlapping clinical indications for R14.

Added psychiatry as a requesting specialty as separate Clinical Indication for Intellectual Disability has been retired.
R29 Intellectual disability (WGS) Clinical indication retired.  Patients to be tested under R27 Paediatric disorders where patients meet the criteria for R27.
R377 Intellectual disability – microarray only Clinical indication retired.  Patients to be tested under R27 Paediatric disorders where patients meet the criteria for R27.
R48 Prader-Willi syndrome Additional criteria added to promote appropriate referrals.
R69 Hypotonic infant Addition of R452 Silver Russel Syndrome / Temple syndrome to overlapping CIs.

Removal of confirmatory STR CITT R69.6 as the generic code for confirmation test should be used instead.
R code Clinical indication name Summary of changes
R314 Ambiguous genitalia Changed name of Clinical Indication by removing “presenting neonatally”.

Amended the criteria that includes non neonatal presentations.
R142 Glucokinase-related fasting hyperglycaemia Added specialist midwifery to the requesting specialties.
R146 Differences in sex development Removed R297 as an overlapping clinical indication as R297 has been retired (see separate entry) and added R468 Possible sex chromosome aneuploidy or structural rearrangement – Targeted Chromosome Analysis, as new overlapping CI.
R452 Silver Russell Syndrome and Temple Syndrome Added to the testing criteria, clinical features suggestive or Temple Syndrome for different age groups.
R453 Monogenic short stature Added table of primary investigations in children referred to secondary and tertiary care with short stature from the British Society for Paediatric Endocrinology and Diabetes recommendations.

Added clarifying statement in the overlapping clinical indications for R52 Short stature – SHOX deficiency.  To state that this test should be ordered if you suspect SHOX deficiency as SHOX is not include on the panel test for R453 due to technical limitations.
R267 Temple syndrome – maternal uniparental disomy 14 Retired Clinical Indication. Patients to be tested under R452 Silver Russell Syndrome and Temple Syndrome, where they meet the testing criteria.
R180 Congenital adrenal hyperplasia diagnostic test Added an additional criterion in the testing criteria:

Female adult with raised 17-OHP and at least one of the following: hirsutism, frontal baldness, delayed menarche or infertility.
R388 Linkage testing for congenital adrenal hyperplasia Retired Clinical Indication as the generic code for linkage testing should be used instead, R409 Linkage testing for recognisable Mendelian disorders.
R293 Albright hereditary osteodystrophy, pseudohypoparathyroidism pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis Added Paediatrics as a requesting specialty
R154 Hypophosphataemia or rickets Criteria added to the testing criteria for patients with low ALP that requires one of the following:

  • early dental loss OR
  • rickets-like changes on X-ray OR
  • chronic musculoskeletal pain OR
  • atypical femoral fractures OR
  • poor healing fractures
R223 Inherited phaeochromocytoma and paraganglioma excluding NF1 Removed from the 6th testing criteria “renal cell cancer (any age)”.
R158 Lipodystrophy Amended the Clinical Indication name FROM Lipodystrophy – childhood onset TO: Severe insulin resistance and lipodystrophy syndromes.

Amended testing criteria to remove need for childhood onset and added in severe insulin resistance.

Additional genes added to the panel to align with these changes.
R code Clinical indication name Summary of changes
R445 Common aneuploidy testing – NIPT Amended Clinical Indication name

FROM: Common aneuploidy testing – NIPT

TO: T21, T18, T13 aneuploidy testing – NIPT (previous history).

Amended testing criteria to specify the three aneuploidy syndromes that are tested for.

Made amendments to criteria so that R445 and R470 (new CI) are aligned.
R470 T21, T18, T13 aneuploidy testing – NIPT NHS Fetal Anomaly Screening Programme (FASP) New Clinical Indication.
R318 Recurrent miscarriage with products of conception available for testing Removed R297 as an overlapping clinical indication as R297 has been retired (see separate entry) and added R464 Recurrent miscarriage where products of conception are not available for testing – parental karyotype, as a new overlapping Clinical Indication.
R22 Fetus with a likely chromosomal abnormality Added to the criterion for death or stillbirth from 24 weeks to clarify this is referring to intrauterine death.
R304 NIPD for cystic fibrosis – haplotype testing Error correction, removal of “where parents are consanguineous” from criterion 1.
R306 NIPD for Apert syndrome – variant testing Removed from criteria testing where there has been a previous pregnancy with confirmed Apert syndrome.
R307 NIPD for Crouzon syndrome with acanthosis nigricans – variant testing Removed from criteria testing where there has been a previous pregnancy with confirmed Crouzon syndrome.
R308 NIPD for FGFR2-related craniosynostosis syndromes – variant testing Removed from criteria testing where there has been a previous pregnancy with confirmed FGFR2 related craniosynostosis.
R309 NIPD for FGFR3-related skeletal dysplasias – variant testing Removed from criteria testing where there has been a previous pregnancy with confirmed FGFR3 related skeletal disorder.
R433 NIPD for monogenic diabetes, subtype glucokinase Amended Clinical Indication name

FROM: NIPD for monogenic diabetes, subtype glucokinase

TO: Monogenic diabetes, subtype glucokinase – NIPT
R code Clinical indication name Summary of changes
R177 Hirschsprung disease Retired Clinical Indication.  Patients to be tested under R438 Paediatric pseudo-obstruction syndrome, where they meet the testing criteria.
R438 Paediatric pseudo-obstruction syndrome Added to “where in pathway”:

“This test should be used where testing for Hirschsprung disease is required”.
R code Clinical indication name Summary of changes
R208 Inherited breast cancer and ovarian cancer Error correction: removal of need to reach criteria 2 in the criterion 4b.
R210 Inherited MMR deficiency (Lynch syndrome) Amended the Lynch related cancers for sebaceous adenomas and carcinoma so that it now reads:

at least two sebaceous adenomas, one or more sebaceous carcinoma.  A single sebaceous adenoma does not constitute a Lynch-related cancer.

Amendment to the sentence above the table of associated tests to now read:

Please note that not all the associated tests will be undertaken in every case.  The clinical presentation will indicate the tests that are necessary.
R211 Inherited polyposis and early onset colorectal cancer – germline test Gynaecology added to requesting specialties.
R414 APC Associated Polyposis Additional 8th criteria added to the testing criteria and change to criteria 7.

Removal of R359 Childhood solid tumour panel, from overlapping clinical indications as R359 has been retired, see separate entry for the details.

Added dermatology to requesting specialties.
R215 Hereditary diffuse gastric cancer Amendments to criteria 1e, 1g and 1h.
R359 Childhood solid tumours Retired Clinical Indication.  Two new Clinical Indications replace R359.  These are R456 and R457.  Testing should only be ordered under codes R456 and R457 where patients meet the testing criteria for these new Clinical Indications.
R220 Wilms tumour with features suggestive of predisposition Retired Clinical Indication.  Patients should be tested under the new Clinical Indication R456.
R358 Familial rhabdoid tumours Retired Clinical Indication.  Patients should be tested under the new Clinical Indication R456.
R456 Embryonal tumour of possible germline origin New Clinical Indication.
R457 Sarcoma of possible germline origin New Clinical Indication.
R224 Inherited renal cancer Amendments to criteria 2. and 6.
R254 Familial melanoma Various changes to the testing criteria.
R365 Fumarate hydratase-related tumour syndromes Amendment to criteria b.
R444 NICE approved PARP inhibitor treatment Amendments to criteria R444.1 for breast cancer to align with updated CDF criteria.
R code Clinical indication name Summary of changes
R450 Diagnostic testing for Isovaleric acidaemia Confirming in the criteria that genetic testing is only where required as part of the diagnostic testing pathway.

Removal of the sentence:

In the case of isovaleric acidaemia, this means that testing is almost exclusively used at those in whom biochemical results indicate a likely pseudodeficiency allele is present.
R code Clinical indication name Summary of changes
R315 POLG-related disorder Removal of R59 as overlapping clinical indication as R59 is retired.  Addition of R27 as an overlapping Clinical Indication with note that this should be used, or other relevant broader test, where clinical features are not strongly suggestive of POLG-related disorder and a broader differential diagnosis is under consideration.
R code Clinical indication name Summary of changes
R297 Possible structural chromosomal rearrangement – karyotype or Targeted Chromosome Analysis Clinical Indication retired and replaced with separate Clinical Indications for each of the clinical scenarios where R297 would have been requested.  The new Clinical Indications are; R463, R464, R465, R466, R467 and R468
R463 Cytogenetic characterisation of a genomic abnormality – Karyotype or Targeted Chromosome Analysis New Clinical Indication
R464 Recurrent miscarriage,  products of conception not available – parental karyotype New Clinical Indication
R465 Familial cytogenetic rearrangement – Karyotype or Targeted Chromosome Analysis New Clinical Indication
R466 Unexplained infertility – karyotype New Clinical Indication
R467 Gamete donors – karyotype New Clinical Indication
R468 Possible sex chromosome aneuploidy or structural rearrangement – Targeted Chromosome Analysis New Clinical Indication
R298 Possible structural or mosaic chromosomal abnormality – FISH Removal of R297 as an overlapping Clinical Indication as this has been retired.  Addition of two new Clinical Indications in overlapping Clinical Indications; R463 and R465.
R code Clinical indication name Summary of changes
R104 Skeletal dysplasia Addition to the testing criteria to clarify that isolated short stature, without evidence of an underlying abnormality of the bones is not appropriate to test via this indication.  Other overlapping indications may be more appropriate in these cases.

Overlapping Clinical Indications added:

  • R453 Monogenic short stature
  • R52 Short stature – SHOX deficiency
  • Requesting specialties added:
  • Paediatrics
  • Endocrinology
R415 Cleidocranial dysplasia (CCD) Clinical indication retired.  Patients to have R104 testing instead, where they meet the testing criteria.
R101 Ehler Danlos syndrome with a likely monogenic cause Additional testing criteria has been added and states that testing should NOT be used to exclude a diagnosis.

Overlapping clinical indication added:

R125 Thoracic aortic aneurysm or dissection panel includes the COL1A1, COL3A1, COL5A1, COL5A2, PLOD1 and FKBP14 genes and may be a better option for patients presenting with aortic/arterial dilatation or rupture without additional features of EDS. Clarification may be sought from the highly specialised National Ehlers Danlos services:

[email protected]  or [email protected]
R102 Osteogenesis imperfecta Addition to the testing criteria:

Referrals where non-accidental injury is suspected should be discussed with the OI Highly Specialised Service before requesting genomic testing
R284 Van der Woude syndrome Clinical indication retired.  Patients to have R27 testing instead, where they meet the testing criteria.
R code Clinical indication name Summary of changes
R471 Neurodegenerative Disorders, adult onset – Prenatal Exclusion Testing New Clinical Indication
R55.5

R56.4

R57.6

R60.4

R61.5

R78.6

R381.4

R84.5

 Confirmatory STR testing for various neurology clinical indications Retired Clinical Indication Test Types. Codes R55.5, R56.4, R57.6, R60.4, R61.5, R78.6, R381.4 and R84.5 are no longer in use. The multi purpose test R443 Confirmation test, should be used instead.
R57 Childhood onset dystonia, chorea or related movement disorder Removal of R29 Intellectual disability as an overlapping Clinical Indication.
R58 Adult onset neurodegenerative disorder Retired Clinical Indication.  Testing for the four conditions previously all grouped into this single Clinical Indication have now been separated out into four new Clinical Indications:

  • R458 Young onset or familial dementia,
  • R459 Young onset or complex Parkinson disease,
  • R460 Amyotrophic lateral sclerosis,
  • R461 Cerebral amyloid angiopathy.
R458 Young onset or familial dementia New Clinical Indication, replacing R58.
R459 Young onset or complex Parkinson disease, New Clinical Indication, replacing R58.
R460 Amyotrophic lateral sclerosis New Clinical Indication, replacing R58.
R461 Cerebral amyloid angiopathy New Clinical Indication, replacing R58.
R59 Early onset or syndromic epilepsy Retired Clinical Indication.  Patients who meet the testing criteria for R27 should have this testing instead.  The genes for the R59 panel are already on R27.
R378 Linkage testing for Duchenne or Becker muscular dystrophy Retired Clinical Indication.  The multi purpose test R409 Linkage testing for recognisable Mendelian disorders, should be used instead.
R82 Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies Addition to where in the pathway that provides information about the Highly Specialised Service.
R85 Holoprosencephaly Change in Clinical Indication name:

FROM: Holoprosencephaly – NOT chromosomal

TO: Holoprosencephaly

Amendments to the testing criteria and to where in the pathway.

Overlapping Clinical Indications added:

  • R27 Paediatric disorders or R89 Ultra-rare and atypical monogenic disorders tests should be used in individuals with congenital malformations, dysmorphism or other complex or syndromic presentations
  • R26 Likely common aneuploidy
  • R28 Congenital malformation and dysmorphism syndromes – microarray
R221 Familial tumours of the nervous system Amendments to the testing criteria.
R222 Neurofibromatosis 1 Additional testing criteria:

  • Axillary/inguinal freckling
  • Malignant Peripheral Nerve Sheath Tumour
R337 CADASIL Removal of R58 from overlapping Clinical Indications.

Addition of R461 Cerebral amyloid angiopathy as an overlapping Clinical Indication where a broader differential diagnosis is under consideration.
R code Clinical indication name Summary of changes
R190 Pneumothorax – familial Testing criteria amendment:

FROM

Primary spontaneous pneumothorax with no identifiable cause, AND one of:

i) A first degree relative with primary spontaneous pneumothorax,

OR

ii) Characteristic radiological features of Birt-Hogg-Dubé syndrome on chest imaging

TO

1. Primary spontaneous pneumothorax with no identifiable cause AND a first degree relative with primary spontaneous pneumothorax,

OR

2. Characteristic radiological features of Birt-Hogg-Dubé syndrome on chest imaging
R192 Surfactant deficiency Retired Clinical Indication.  Patients should be tested for R462 Childhood interstitial lung disease, where they meet the testing criteria.
R462 Childhood interstitial lung disease New Clinical Indication.
R code Clinical indication name Summary of changes
R239 Incontinentia pigmenti  Addition to the testing criteria to reference IKBKG- related immunodeficiency.

Addition to requesting specialties:

Immunology (+/- Paediatrics).
R code Clinical indication name Summary of changes
R89 Ultra-rare and atypical monogenic disorders Addition to the testing criteria:

Requests that include any panel for inherited cancers must be taken to the UKCGG/CanGene-CanVar National Multidisciplinary team meeting and receive delegate approval to proceed.
R code Clinical indication name Summary of changes
R370 Validation test Change of name:

FROM: Validation test

TO: Validation of unaccredited findings

Additional clarification is provided in the testing criteria as to when this test should be used.
R443 Confirmation test Expansion of testing criteria to clarify when this Clinical Indication should be used.

Change in requesting specialties so that only genomics laboratory is the requestor.
R447 Diagnostic discovery – validation/confirmation findings Change of name:

FROM: Diagnostic discovery – validation/confirmation of findings

TO: Validation of WGS Diagnostic discovery findings