Phenotypic spectrum and molecular characteristics of variants of uncertain significance in copy number variations associated with fetal cardiac malformations: a case series of 9 patients

Although VUS-CNVs are uncommon in fetuses with CHMs, they occur more frequently in non-isolated phenotypes and carry the potential for future reclassification-posing significant challenges in prenatal genetic counseling. These two aspects underscore the necessity of trio-based genomic testing, cautious interpretation of results, and longitudinal follow-up. Given the limited sample size of this study, no causal relationship between VUS-CNVs and clinical phenotypes can be inferred; however, our findings support a risk-stratified management framework that integrates detailed fetal phenotyping, trio analysis, and postnatal follow-up to enable accurate variant interpretation and informed decision-making.