This Clinical Indication relates to carrier testing in partners of individuals who are affected with, or are known
carriers with a family history 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 R448 Prenatal
Testing
or
• carrier testing of a partner is feasible and will inform/determine clinical management (including
surveillance) for their children.
This Clinical Indication is not intended to influence decision making, related to reporting of incidental carrier
findings in genes associated with autosomal recessive disorders, in individuals without a personal or family
history. It is only relevant to partners of affected individuals or partners of carriers detected through targeted
testing due to family history.
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/or
there are early detection/screening strategies available to biallelic offspring and carrier testing is feasible.
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
3. Presence of a biallelic genotype in the couple’s offspring would result inform/determine clinical
management e.g. early detection and/or prevention strategies.
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.
395 v7.1 January 2025
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
• R185 Cystic fibrosis carrier testing