As we continue to discover the genetic causes for human disease, we are seeing that pathogenic alterations in one gene can have varied phenotypic expressions in different individuals. This commonly was attributed to “genotype-phenotype correlations” or simply to “variable expressivity”, but another explanation is that one gene can cause two distinct genetic disorders. How can one distinguish between simple “variable expressivity” and a gene that is causative of two distinct disorders? We will discuss the types of information that is used to differentiate between spectrum and allelic disorders and investigate how to use this distinction to improve and clarify variant classification.
Level of Instruction: Intermediate