{"doi":"10.1101/2025.01.25.25321117","title":"Insights on improving accessibility and usability of functional data to unlock its potential for variant interpretation","abstract":"Introduction: Variant-level functional data is a core component of clinical variant classification and can aid in reinterpreting variants of uncertain significance (VUS). However, the usage of functional data by genetics professionals is currently unknown. Methods: An online survey was developed and distributed in spring of 2024 to individuals actively engaged in variant interpretation. Quantitative and qualitative methods were used to assess responses. Results: 190 eligible individuals responded, with 93% reporting interpreting 26 or more variants per year. The median respondent reported 11-20 years of experience. The most common professional roles were laboratory medical geneticists (23%) and variant review scientists (23%). 77% reported using functional data for variant interpretation in a clinical setting and overall respondents felt confident in assessing functional data. However, 67% indicated that functional data for variants of interest was rarely or never available, and 91% considered insufficient quality metrics or confidence in the accuracy of data as barriers to its use. 94% of respondents noted that better access to primary functional data and standardized interpretation of functional data would improve usage. Respondents also indicated that handling conflicting functional data is a common challenge in variant interpretation that is not performed in a systematic manner across institutions. Discussion: The results from this survey showed a demand for a comprehensive database with reliable quality metrics to support use of functional evidence in clinical variant interpretation. The results also highlight a need for guidelines regarding how putatively conflicting functional data should be used for variant classification.","journal":"medRxiv","year":2025,"id":555952,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7412,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":759782,"name":"Runjun D. Kumar","orcid":"0000-0001-7369-5956","position":1,"is_corresponding":false},{"id":1381143,"name":"Cristian Ovadiuc","orcid":null,"position":2,"is_corresponding":false},{"id":1381144,"name":"Andrew Folta","orcid":null,"position":3,"is_corresponding":false},{"id":667487,"name":"Abbye E. McEwen","orcid":"0000-0001-7187-7975","position":4,"is_corresponding":false},{"id":1320834,"name":"Ashley Snyder","orcid":"0000-0002-1980-2092","position":5,"is_corresponding":false},{"id":262399,"name":"Douglas M. Fowler","orcid":"0000-0001-7614-1713","position":6,"is_corresponding":false},{"id":561883,"name":"Alan F. Rubin","orcid":"0000-0003-1474-605X","position":7,"is_corresponding":false},{"id":286047,"name":"Brian H. Shirts","orcid":"0000-0002-7188-6764","position":8,"is_corresponding":false},{"id":95807,"name":"Lea M. Starita","orcid":"0000-0003-2870-5099","position":9,"is_corresponding":false},{"id":11629,"name":"Andrew B. Stergachis","orcid":"0000-0002-1299-3674","position":10,"is_corresponding":false},{"id":1380669,"name":"Min Seon Park","orcid":"0000-0003-1172-9967","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:55:03.976486Z","pmid":"39974143","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}