MSH3 germline biallelic pathogenic variants

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

ID	`BIO-MSH3-GERMLINE`
Type	Biomarker
Aliases	MSH3 germline pathogenic variant (biallelic)MSH3 germline біалельні патогенні варіанти
Status	reviewed 2026-05-18 \| pending_clinical_signoff
Diseases	`DIS-CRC`
Sources	`SRC-NCCN-GENETIC-FAMILIAL-CRC-2025`

Biomarker Facts

Biomarker type	gene_mutation
Mutation details	{"functional_impact": "loss_of_function", "gene": "MSH3", "gene_hugo_id": "HGNC:7326", "variant_type": "missense_or_truncating"}
Related biomarkers	None declared

Notes

MSH3 germline biallelic — drives MSH3-associated polyposis (autosomal recessive). MutSbeta mismatch-repair component; biallelic loss → elevated-microsatellite-alterations-at-selected-tetranucleotide-repeats (EMAST) phenotype rather than classic MSI-H. Adenomatous polyposis + CRC (typically attenuated, later-onset than FAP), with reported duodenal adenomas, gastric, and astrocytomas. Distinct from Lynch syndrome (heterozygous MMR genes). Heterozygotes near population risk. Surveillance under NCCN polyposis schedule. STUB pending two-Co-Lead signoff.

Used By

Actionability

BMA-MSH3-GERMLINE-POLYPOSIS-BIALLELIC - MSH3 germline biallelic pathogenic variants cause MSH3-associated polyposis (Adam et al....