This Clinical Indication relates to carrier testing in partners of individuals who are affected with, or are known
carriers of, an autosomal recessive condition, where management of a current or future pregnancy would be
impacted by the result, and the couple would be eligible either for PGD, or for prenatal diagnosis under the
clinical indication R240 Diagnostic testing for known mutation(s).
In most autosomal recessive conditions, cascade testing of wider family members and unrelated
partners is NOT indicated. Clinicians wishing to request a test under this indication should check
with their GLH whether the test is feasible prior to offering testing to patients.
Testing is not usually indicated in this context because the test results have a minimal impact on the risk of health problems in pregnancies beyond the parents and siblings of the affected individual:
1. For most genes, interpreting the results of population risk carrier testing is complex, and the
proportion of detected variants which can be confidently used for reproductive purposes is low
2. Carrier testing at population risk is not able to rule out an unrelated partner being a carrier of the condition, only reduce the likelihood
3. The carrier frequency of most autosomal recessive conditions is low, such that the marginal gain from genetic testing of an unrelated partner has limited impact on the prenatal decision-making process

However, there are circumstances in which the chance of a baby being affected is more substantial, and carrier testing is possible. Testing is more likely to be considered appropriate where the following criteria are met:
1. Presence of a homozygous or compound heterozygous genotype in a baby would have a sufficiently predictable effect to permit reproductive choices to be made; for example, carrier testing for haemochromatosis or alpha-1-antitrypsin deficiency is NOT appropriate as it is not possible to predict from the genotype whether an affected baby will ever develop medical problems
2. The associated gene is well-understood and does not contain a high level of novel, benign variation, such that it is likely to be possible to interpret variants found on full gene testing in individuals at population risk; in this context only likely pathogenic or pathogenic variants according to the ACGS / ACMG classification will be reported

PLUS one of the following:
1. The carrier frequency of the condition is higher than 1 in 70 (in the relevant population(s) for the
patient to be tested)
2. The couple are consanguineous (second cousins or closer); where this is the only criterion that is met, testing will be limited to the known familial variant.

In exceptional circumstances and after discussion with the home GLH, testing may be considered appropriate in situations where the gene is suitable for testing and there are known pathogenic variant(s), that can be tested for, that account for the majority of cases in the relevant population(s) for the patient to be tested; in this context, the test will primarily target the pathogenic variants that account for the majority of cases in the relevant population(s).

NOTE: The following specific clinical indications should be used instead for the relevant disorders:
• R181 Congenital adrenal hyperplasia carrier testing
• R361 Haemoglobinopathy trait or carrier testing
• R362 Carrier testing for sickle cell disease
• R252 SMA carrier testing at population risk for partners of known carriers
• R105 MCADD – Medium-chain acyl-CoA dehydrogenase deficiency – common variant
• R185 Cystic fibrosis carrier testing