The possibility of a second contributing diagnosis ought to considered for all if phenotype differs from the "usual"

GRADE IGRADE IIGRADE III
  • Pathogenic anomaly
  • Strong agreement amongst geneticists
  • Highly penetrant
  • May still have variable phenotype but some common features
  • All cases in the literature have a clinical phenotype
  • No cases of health individuals with this anomaly
  • Not reported on DVG databases or found in healthy population
  • Functional data confirming single gene or multigene dosage effect
  • Confirmed or strong candidate genes
  • Clinical management implications defined
  • Known cancer risk with implication for surveillance
  • Multiple sources of information (OMIM, Genereviews, Orphanet, Unique, Wikipedia)
  • Available for diagnostic use (reproductive counselling)
  • Likely pathogenic anomaly
  • Highly penetrant
  • Variable phenotype with no consistent features other than DD
  • Small number of cases/ reports in the literature
  • All reported cases have a clinical phenotype
  • No functional data or confirmed pathogenic genes
  • Multiple sources of information (OMIM, Genereviews, Orphanet, Unique, Wikipedia)
  • May be used for diagnostic purposes and reproductive counselling
  • Susceptibility Locus
  • Healthy individuals or unaffected parents of a patient described
  • Present in control popualtions
  • Non penetrance
  • Phenotype mild and not specific
  • Features less consistent
  • No functional data or confirmed pathogenic genes
  • More limited sources of data
  • Possibility of second diagnosis remains a possibility for cases deviating from the majority or if novel clinical finding present
  • Caution when using for diagnostic purposes and guarded advice for reproductive counselling