ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
14635101 Taylor et al (2003) screen 215 subjects referred to a clinic for phenotype consistent with autosomal dominant familial nonpolyposis colon cancer (Lynch Syndrome) and identify 6 MLH1 deletions (as well as 10 novel MLH1 mutations.)
15942939 van der Klift (2005) screened a large cohort of families with hereditary nonpolyposis colon cancer and identified 13 MLH1 deletions from 68 unrelated kindreds.

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.