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Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Some comments on "assessing clinical significance"
Z Martinovich1, S Saunders, K Howard
1a Northwestern University.
Abstract:
The strategies for extending clinical significance (CS) methodology, suggested by Tingey et al., have considerable merit. They also serve to highlight the difficulties encountered with CS methodology in general. Problems encountered with the original methodology may be compounded, not solved, by such extensions. For example, problems around lack of agreement about the appropriateness of certain measures, and the questionable psychometric properties of measures, are likely to be exacerbated, not lessened, when attempting to measure social impact. Similarly, the proposal that multiple normative groups be identified to provide the impact factor does not resolve the original difficulty of identifying and discriminating more obviously diverse groups, such as functional and dysfunctional. Other problems with the proposed extensions, such as using criterion "c" (Jacobson and Truax, 1991) with non-normal distributions, are discussed. Some recommendations regarding these problems are made.
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