Must love rules: an insider’s guide to variant sciences

Unknown significance. Quite possibly the two most dreaded words in clinical genetics. To some these two words should seldom be used let alone act as qualifiers for testing results. What are the rules of assessment? How do laboratories determine what constitutes enough evidence to say that a variant, previously known as mutation, is of known significance?   Continue reading

Remembering the five Ps: how to interpret genetic variants in epilepsy

Epilepsiome. Two weeks ago, we had a few teleconferences about what the purpose of our gene curation and gene review efforts should be. Should we be a blog, should we be OMIM, or should we be a new neuromuscular homepage?  None of these resources feel quite right for the questions that we have in epilepsy genetics. While thinking about this question, it became clear to me that we need to address five different aspects of each epilepsy gene, a framework that I’ll refer to as the 5-P concept. What is this concept about? Follow me onto a journey into the essential dimensions of interpreting the relevance of a variant in a clinical context. Continue reading