Reclassification Is All You Missed: Surfacing Variant Reinterpretation Need in Online Health Communities at Population Scale

Researchers built PRISM, an agentic large-language-model pipeline that screened 3.9 million posts across 32 online health communities and surfaced 123 candidate genetic-variant classification differences, 5 of them involving a shift from an uncertain submission to pathogenic or likely pathogenic, according to the arXiv paper 2611.07054v1. Agent-predicted reinterpretation-relevant discussion was rare at 0.288% overall but concentrated in specialist genetics communities at 6.30% versus 0.10% in general medical-advice communities, and grew fivefold since 2014. In a held-out set of 30 real-post drafts, a clinician judged 27 factually grounded and 15 fit to send, leading the authors to conclude factual accuracy is necessary but not sufficient for clinically acceptable outreach.

arXiv:2611.07054v1 Announce Type: new Abstract: Genetic variants are routinely reclassified in ClinVar after a patient is tested, sometimes from uncertain to pathogenic, yet patient recontact is inconsistent, with no clear duty and responsibility diffused among labs, providers, and patients. Many affected people discuss their results in public online health communities that clinical recontact often does not reach. We built PRISM, an agentic large-language-model pipeline that screens these posts, checks whether the variant was later reclassified, and drafts a disclaimer-bearing outreach message, in a no-contact dry run. Across 3.9 million posts from 32 communities, agent-predicted reinterpretation-relevant discussion is rare 0.288% but concentrated in specialist genetics communities 6.30% versus 0.10% in general medical-advice communities and growing fivefold since 2014; PRISM surfaces 123 candidate classification differences, 5 of them from an uncertain submission to pathogenic or likely pathogenic. On a held-out set of 30 real-post drafts, a clinician judged 27 factually grounded and 15 fit to send: factual accuracy is necessary but not sufficient for clinically acceptable outreach. PRISM contributes a population-scale reinterpretation-need map with code and data to be released upon publication.