Return the metadome-link discovery surface: identity/build/MetaDome data version, the frozen tool list, response modes, recommended workflows, the error taxonomy, and limits. detail='full' adds the score/async semantics and policy notes. Call this first in a cold session, or read metadome://capabilities / metadome://tools. Signature: get_server_capabilities(detail=, response_mode=).

Report local runtime health WITHOUT calling MetaDome: build info, result-cache stats (on-disk + LRU sizes, pinned data version), the runtime metrics snapshot (request/error counts + latency percentiles), the data versions, and the capabilities hash. Use this to confirm cache state or diagnose a misconfigured server. Signature: get_diagnostics(response_mode=).

Resolve a gene symbol or versioned Ensembl transcript id to MetaDome GRCh37 transcript candidate(s). A gene symbol returns all transcripts sorted by protein length (aa_length descending) with the longest protein-coding entry flagged canonical. A bare ENST id (version suffix required) is validated and echoed directly. Use the canonical_transcript_id with request_tolerance_landscape to start a tolerance-landscape build. Signature: resolve_transcript(query=, response_mode=).

Submit (or re-confirm) a MetaDome tolerance-landscape build for a versioned transcript and return a poll handle. status='ready' means the landscape is pre-built; status='processing' means a cold build is running (up to ~1 hour) -- poll get_tolerance_landscape with poll_after_s until it is ready. Idempotent. Signature: request_tolerance_landscape(transcript_id=, response_mode=).

Return the (cache-first) MetaDome tolerance landscape for a built transcript: Pfam domains plus the paginated per-residue positional_annotation (sw_dn_ds tolerance and upstream annotations). Optional position_start/position_stop slice an inclusive residue range. If the build is still running this returns a first-class status='processing' success -- poll again after poll_after_s. Signature: get_tolerance_landscape(transcript_id=, position_start=, position_stop=, limit=, offset=, response_mode=).

Return one residue's missense tolerance (sw_dn_ds + sliding-window coverage), its Pfam/meta-domain membership, and explicitly scoped variant evidence on a built tolerance landscape. Out-of-range positions raise invalid_input; a not-yet-built landscape raises not_found (request_tolerance_landscape first). Signature: get_position_tolerance(transcript_id=, position=, response_mode=).

Return residue-level ClinVar annotations and explicitly-labelled Pfam homolog aggregates on a built landscape, filtered by source (both|gnomad|clinvar). MetaDome has no true residue-level gnomAD count, so it is marked unavailable, never zero. Accepts one position, an inclusive range, or the whole protein (paginated); ClinVar variants include NCBI urls. Signature: get_variant_counts(transcript_id=, position=, position_start=, position_stop=, source=, limit=, offset=, response_mode=).

Return a side-by-side tolerance table (sw_dn_ds, ref_aa, domain ids, explicitly scoped variant evidence) for a batch of residue positions on a built landscape. Out-of-range positions get a per-item error row -- the whole batch never fails for one bad position; the batch size is capped. Signature: compare_positions(transcript_id=, positions=, response_mode=).

List the Pfam protein domains annotated on a transcript's tolerance landscape: each domain's ID, Name, start/stop residues, whether a meta-domain (homologous) mapping exists, and its alignment depth. Requires a built landscape (call request_tolerance_landscape first). Signature: get_protein_domains(transcript_id=, response_mode=).

Return homologous (meta-domain) variant evidence for one residue: gnomAD normal_variants and ClinVar pathogenic_variants observed at the aligned consensus position across the residue's Pfam domain family, each carrying its homolog gene_name. Omit domains to derive the selector from the residue's cached domain mapping; a residue with no meta-domain returns empty lists (not an error). Requires a built landscape. Signature: get_meta_domain(transcript_id=, position=, domains=, limit=, offset=, response_mode=).

Return the top ranked contiguous intolerant regions of a MetaDome tolerance landscape, each annotated with overlapping Pfam domain ids and explicitly scoped variant evidence. Regions are stretches of consecutive residues with sw_dn_ds below threshold (length >= min_run), ranked by mean sw_dn_ds ascending (most constrained first). Signature: summarize_intolerant_regions(transcript_id, threshold=0.5, min_run=3, top_n=15, response_mode='compact').