August 31, 2026
Observation
Why a frameshift doesnt always mean pathogenic
Ask, could translation reinitiation occur, or could the transcript undergo NMD?
Positioning of the variant? could alternative splicing rescue the transcript?
IMPORTANT: check gnomAD pLoF observed/expected, LOEUF and pLI - to check if LoF variants exist in population data , which would potentially weaken the haploinsufficiency argument
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