Copy number variants in germline testing refer to which type of genetic change?

• A. Single base substitutions.
• B. Epigenetic changes.
• C. Deletions or duplications that can be detected by methods like MLPA or microarray.
• D. Balanced translocations.

Answer: (C)

Copy number variants are deletions or duplications of DNA segments that change the number of copies of a genomic region. In germline testing, these structural changes alter gene dosage rather than just the sequence, and they’re detected by methods that measure copy number across the genome or targeted genes, such as MLPA or microarray. This distinguishes them from single base substitutions, which are small sequence changes, and from epigenetic changes, which modify gene expression without changing the DNA sequence, or from balanced translocations, which rearrange material between chromosomes without changing the overall copy number. CNVs are important in hereditary cancer because they can underlie pathogenic variants that sequencing alone might miss.