TTR (Transthyretin) variants and mutations

TTR (also known as Transthyretin) is a human protein-coding gene encoding a transthyretin protein. Its tetramer transports thyroxine and retinol-binding protein, but destabilization can expose aggregation-prone monomers. Pathogenic variants cause hereditary transthyretin amyloidosis affecting peripheral nerves and heart, while wild-type protein can also form cardiac amyloid with aging. This analysis covers 422 TTR variants and mutations. Of these, 94% have computational variant effect predictions. Disease context includes amyloidosis, hereditary systemic 1, cardiomyopathy, and familial amyloid neuropathy. Example TTR variants include A2A, S3S, and H4L.

Variant analysis overview

Variant and mutation evidence

Clinical, disease, and population context

Protein structure and variant hotspots

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable TTR variants

Examples include A2A, S3S, H4L, H4Q, p.His4dup, p.His4del, H4N, R5C. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.