IGHV (immunoglobulin heavy-chain variable region) mutational status

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`BIO-IGHV-MUTATIONAL-STATUS`
Type	Biomarker
Aliases	IGHVIGHV (мутаційний статус варіабельного регіону важкого ланцюга імуноглобуліну)IGHV mutation statusIGHV mutational statusIGHV-mutatedIGHV-unmutated
Status	reviewed 2026-04-25 \| pending_clinical_signoff
Diseases	None declared
Sources	`SRC-NCCN-BCELL-2025`

Biomarker Facts

Biomarker type	gene_mutation
Mutation details	{"functional_impact": "marker of post-germinal-center maturation", "gene": "IGHV (heavy chain variable region — multiple V genes)", "variant_type": "somatic hypermutation status"}
Measurement	MethodPCR + Sanger sequencing of clonal IGHV gene; calculate % germline homology Unitscategorical (mutated <98% germline \| unmutated ≥98% germline)
Related biomarkers	`BIO-CLL-HIGH-RISK-GENETICS`

Notes

Cross-disease relevance: - **CLL/SLL** (primary use): unmutated IGHV (≥98% germline homology) = adverse; mutated = favorable. Historically drove FCR (mutated did well long-term) vs BR (unmutated similar). Modern era: BTKi/VenO work regardless of IGHV status, BUT IGHV-unmutated is one component of the CLL high-risk composite (along with TP53/del 17p/complex karyotype) that drives toward fixed-duration VenO over BTKi continuous in some guidelines. - **MCL** (subset): mutated IGHV in nodal subset (germinal-center-like) behaves more indolently; unmutated in mantle-zone subset more aggressive. Not algorithm-driving currently. - **WM**: IGHV usage informs B-cell ontogeny but not treatment choice. Direct algorithm impact in our KB: triggers RF-CLL-HIGH-RISK when unmutated alone or part of composite. Standalone trigger now wired via this entity.

Used By

Actionability

BMA-IGHV-UNMUTATED-CLL - IGHV mutational status is a fundamental CLL risk stratifier and treatment-selection bioma...

Biomarker

BIO-CLL-HIGH-RISK-GENETICS - CLL high-risk genetics (TP53 / del(17p) / IGHV-unmutated / complex karyotype)

Red flag

RF-CLL-HIGH-RISK - CLL with high-risk genetics: TP53 mutation OR del(17p) OR IGHV-unmutated OR complex karyo...