Mutations c.358G>A and c.2687C>T

Question

Good evening, I have the mutation c.358G>A (exon4) of the cystic fibrosis gene (CFTR) with genotype A120T/NI and my partner has the c.2687C>T.p.Thr896Ile, exon17 T896I of the cystic fibrosis gene LRG_663t1. We were told by the hospital where we had the test that we do not need to do tests in case of pregnancy because they are mild mutations and their combination probably does not create a problem. What do you suggest? Thank you very much.

Answer

The mutations you have:
• You: c.358G>A (p.Ala120Thr) — also known as A120T.
• Your partner: c.2687C>T (p.Thr896Ile) — also known as T896I.
Both mutations:
• are considered mild or of uncertain clinical significance,
• have not been identified in a patient with typical cystic fibrosis.
If the child inherits both variants (one from you and one from your partner), the risk of developing classic cystic fibrosis is considered extremely low to almost zero, because these mutations are not among the “classic pathogens” that cause the disease.
In some cases, such combinations may:
• cause mild manifestations (such as, for example, mild respiratory problems, or infertility in boys — CBAVD),
• or not cause any symptoms.
As long as the mutations you carry are both mild, have low or doubtful pathogenicity and their combination is not considered dangerous for a severe form of Cystic Fibrosis, in case of pregnancy, further prenatal testing specifically for this reason is not considered necessary, unless there are ultrasound findings that are concerning or if you wish it.
Best regards,
M. Poulou

25.04.2025