Genomic testing, variant interpretation, and counselling — branching viva

Opening framework

My framework has four layers. First, the test and its yield — the hierarchy from karyotype through chromosomal microarray (first-tier for unexplained developmental disability, 10 to 20 percent yield) to exome sequencing (25 to 40 percent) and genome sequencing (40 to 50 percent). Second, the variant and its classification — the ACMG/AMP five-tier framework that converts raw sequence data into a probabilistic call, distinguishing pathogenic from uncertain from benign. Third, the counselling — the pre-test conversation that covers yield, VUS possibility, secondary findings, and consent, and the post-test disclosure that contextualises the result. Fourth, the family — cascade testing of parents, siblings, and at-risk relatives, and periodic re-analysis as knowledge grows. ^{[1] [9]}