2026-10-12T09:35:55Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34036136 2026-09-30T17:44:25Z category_7 category_13 category_14 category_15 category_21 category_272 category_734 category_811 category_132 category_133 portal_5 item_type_1 month_year_09_2026

<p>The percentage of variants above folding free energy thresholds.</p> Rose A. Gogal (25145417) Genevieve M. Cox (25145420) Diana L. Kolbe (25145423) Amanda M. Odell (25145426) Chloe E. Ovel (25145429) Katherine I. McCormick (25145432) Brian Hong (9094275) Hela Azaiez (713978) Thomas L. Casavant (10476490) Richard J. H. Smith (10957842) Terry A. Braun (18231361) Michael J. Schnieders (1782085) Medicine Genetics Molecular Biology Neuroscience Biotechnology Environmental Sciences not elsewhere classified Biological Sciences not elsewhere classified Mathematical Sciences not elsewhere classified Infectious Diseases Plant Biology world &# 8217 patient &# 8217 identify twelve probands clinvar 2019 dataset highlight two variants deafness variation database higher prior probability dvd dataset demonstrates missense variation based computational evidence based labeled dvd variants 752 missense variants 237 missense variants deafness associated vus protein folding stability 7 %) genes least 2 kcal intolerant dvd genes deafness variants 7 %) vus ). posterior probability 752 ). 237 ). 0 kcal uncertain significance three bins simpler versions public resource protein misfolding probabilistic frameworks genetic diagnosis biophysical rationale biophysical characterization best accuracy bayesian model amp recommendations also offering 577 classified <p>Panel A shows the number (left axis, solid lines) and fraction (right axis, dashed lines) of labeled variants that are pathogenic (containing likely pathogenic and pathogenic) and benign (containing likely benign and benign) with a predicted value above the threshold defined by the X-axis. Panel B focuses on the number (left axis, solid lines) and fraction (right axis, dashed lines) of VUS that reach either the strong posterior (0.6) or very strong posterior (0.98) with a value above the threshold defined by the X-axis. Panel C plots the percentage of variants that with value above a series of thresholds for labeled variants and for the VUS above the posterior of 0.98. Panel D shows the genes where at least 50% of their LP/P variants have a of at least 1 kcal/mol. Genes with less than 50% of their pathogenic variants above the threshold are included in Fig E in the <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1012085#pgen.1012085.s001" target="_blank">S1 Appendix</a>. Any genes with less than 10 labeled pathogenic/likely pathogenic variants are excluded from this analysis.</p> 2026-09-30T17:56:54Z Image Figure 10.1371/journal.pgen.1012085.g006 https://figshare.com/articles/figure/_p_The_percentage_of_variants_above_folding_free_energy_thresholds_p_/34036136 CC BY 4.0