ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000005.9) (NC_000005.10)

Haploinsufficiency phenotype comments:

Biallelic variants in MSH3 are found to be associated with autosomal recessive Familial adenomatous polyposis in 2 pairs of sibs from 2 unrelated families (Am. J. Hum. Genet. 99: 337-351, 2016, PMID 27476653). Three patients were diagnosed with polyps in their thirties; the fourth patient was diagnosed with colorectal adenocarcinoma at age 56. The 3 older patients, including both probands, had additional significant proliferative disorders affecting other organs, including thyroid adenoma, duodenal polyps, intraductal papillomas of the breast, uterine myoma, cutaneous fibrolipoma, astrocytoma, and gastric carcinoma. The reported variants were either loss of function or splice changes(c.1148delA, c.2319-1G>A, c.2760delC, and c.3001-2A>C). Immunohistochemical staining illustrated a complete loss of nuclear MSH3 in normal and tumor tissue.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

no evidence for triplosensitivity