title: Systematic Classification of Disease Severity for Evaluation of Expanded Carrier Screening Panels.
abstract: Professional guidelines dictate that disease severity is a key criterion for carrier screening. Expanded carrier screening, which tests for hundreds to thousands of mutations simultaneously, requires an objective, systematic means of describing a given disease's severity to build screening panels. We hypothesized that diseases with characteristics deemed to be of highest impact would likewise be rated as most severe, and diseases with characteristics of lower impact would be rated as less severe. We describe a pilot test of this hypothesis in which we surveyed 192 health care professionals to determine the impact of specific disease phenotypic characteristics on perceived severity, and asked the same group to rate the severity of selected inherited diseases. The results support the hypothesis: we identified four "Tiers" of disease characteristics (1-4). Based on these responses, we developed an algorithm that, based on the combination of characteristics normally seen in an affected individual, classifies the disease as Profound, Severe, Moderate, or Mild. This algorithm allows simple classification of disease severity that is replicable and not labor intensive.
authors.affiliation: Counsyl, South San Francisco, California, United States of America.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Lazarin
authors.affiliation: Counsyl, South San Francisco, California, United States of America.
authors.forename: Felicia
authors.initials: F
authors.lastname: Hawthorne
authors.affiliation: Counsyl, South San Francisco, California, United States of America.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Collins
authors.affiliation: Counsyl, South San Francisco, California, United States of America.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platt
authors.affiliation: Counsyl, South San Francisco, California, United States of America.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Evans
authors.affiliation: Counsyl, South San Francisco, California, United States of America.
authors.forename: Imran S
authors.initials: IS
authors.lastname: Haque
mesh_terms: D000465:Algorithms; D006580:Genetic Carrier Screening / Q000379:methods*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008403:Mass Screening / Q000379:methods*; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires