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A young adult presented with pleomorphic rhabdomyosarcoma and a family history of colorectal cancer. Comprehensive cancer genomic profiling of the tumor revealed a heterozygous germline frameshift in MSH2, c.1741delA (p.Ile581LeufsTer9), implicating mismatch repair deficiency in this rare manifestation of Lynch syndrome (PMID:35260566). No additional unrelated cases or segregation data are reported, and rhabdomyosarcoma is not a typical Lynch spectrum tumor.
Clinical validity is Limited based on a single proband without family segregation or replication. Genetic evidence is Limited: one LoF variant in MSH2 identified in a single case ([PMID:35260566]). Functional evidence is Limited: no disease‐specific assays, although MSH2’s role in DNA mismatch repair and interaction with p53 is established but not tested in rhabdomyosarcoma context.
Key Take‐home: Germline MSH2 pathogenic variants may rarely predispose to rhabdomyosarcoma, but further cases and functional studies are required before clinical implementation.
Gene–Disease AssociationLimitedSingle unrelated proband, no segregation or replication Genetic EvidenceLimitedOne LoF MSH2 variant reported in a single rhabdomyosarcoma case ([PMID:35260566]) Functional EvidenceLimitedNo rhabdomyosarcoma‐specific functional assays; general MSH2 mismatch repair function known |