Background: TTN-related limb-girdle muscular dystrophy R10 (LGMDR10) is a rare autosomal recessive neuromuscular disorder caused by biallelic pathogenic variants in the TTN gene. Owing to the large size of TTN and the marked phenotypic heterogeneity of titinopathies, molecular diagnosis can be challenging. Accurate genetic diagnosis is essential for reproductive risk assessment and prenatal genetic counselling. We report the successful application of targeted prenatal diagnosis following molecular confirmation of TTN-related LGMDR10 in an affected father. Case presentation: A 32-year-old pregnant woman with a history of poliomyelitis and two first-trimester pregnancy losses was referred for prenatal genetic counselling because her husband had progressive proximal muscle weakness suggestive of an inherited muscular dystrophy. Expanded carrier screening identified a homozygous pathogenic TTN variant, c.106117C>T (p.Gln35373Ter), confirming TTN-related LGMDR10 in the father. The mother did not carry the familial TTN variant but was heterozygous for pathogenic variants in GYS2 and PNKP and a likely pathogenic variant in DNAAF1. During the ongoing pregnancy, non-invasive prenatal screening indicated a low-risk result. Amniocentesis was subsequently performed for chromosomal microarray analysis and targeted testing for the familial TTN variant. Chromosomal microarray analysis revealed no clinically significant copy number abnormalities, while targeted molecular testing demonstrated that the fetus was heterozygous for the familial TTN variant, indicating carrier status. These findings excluded autosomal recessive TTN-related LGMDR10 in the fetus and enabled accurate genetic counselling regarding recurrence risk and future reproductive options. Conclusions: This case demonstrates the clinical utility of molecular diagnosis in facilitating targeted prenatal testing for TTN-related muscular dystrophy. It further highlights the importance of integrating molecular findings with clinical evaluation, inheritance pattern, and multidisciplinary genetic counselling for accurate prenatal risk assessment and informed reproductive decision-making.