Journal of Molecular Diagnostics最新文献

{"title":"Utility of a Multiplex Molecular Respiratory Pathogen Panel on Clinical Management of Children in the Pediatric Emergency Department","authors":"Samuel M. Goodfellow,&nbsp;Jennifer Dien Bard,&nbsp;Vivian Lee,&nbsp;Deborah R. Liu,&nbsp;Cristina Costales","doi":"10.1016/j.jmoldx.2026.04.005","DOIUrl":"10.1016/j.jmoldx.2026.04.005","url":null,"abstract":"<div><div>Acute respiratory infections in children contribute to a significant volume of pediatric emergency department (PED) visits annually. Rapid molecular respiratory pathogen panels (RPPs) have increasingly been integrated into diagnostic workup. This study aims to investigate RPPs’ impact on clinical management of children presenting to the PED and the effect of implementing restrictive criteria for RPP orders. Retrospective analysis of PED RPP orders from June 2023 through June 2024 was performed with a randomized subset of 400 patients in two cohorts (infants &lt;1 year old and children 1 to 5 years old) selected for in-depth chart abstraction, including clinical presentation and management, with even distribution of RPP-positive and RPP-negative patients. Of 2052 RPPs performed from children age 5 years or younger, 1464 (71.3%) were positive for one or more targets. Regardless of RPP result or patient age, no significant differences in disease severity (mean Emergency Severity Index of 3.7 versus 3.7) or clinical management (infants, 6.0%; young children, 5.0%) were observed. Applying stewardship criteria retrospectively to both cohorts demonstrated a potential 48% reduction in unnecessary testing by RPP. RPP results, positive or negative for one or more targets, had limited impact on clinical management in the PED. The data support the potential value of stewardship intervention to reduce cost while maintaining critical pathogen identification.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"28 7","pages":"Pages 575-582"},"PeriodicalIF":3.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of Multiplex Molecular Tests for Detecting Viral Infections in Lower Respiratory Tract Specimens","authors":"Giuseppe Sberna ,&nbsp;Pierpaolo Paba ,&nbsp;Cosmina Mija ,&nbsp;Gaetana Costanza ,&nbsp;Fabiano Brillo ,&nbsp;Sandro Grelli ,&nbsp;Fabrizio Maggi ,&nbsp;Eleonora Lalle","doi":"10.1016/j.jmoldx.2026.03.008","DOIUrl":"10.1016/j.jmoldx.2026.03.008","url":null,"abstract":"<div><div>Lower respiratory tract (LRT) infections represent a major cause of mortality, particularly among critically ill patients. Molecular diagnostic tests have improved the detection of respiratory pathogens; however, most commercial assays are validated exclusively in upper RT (URT) specimens, limiting their applicability in LRT samples, which better reflect disease severity. This study evaluated the diagnostic performance of two commercially available assays, the BioFire Respiratory Panel 2.1 Plus and the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay, on bronchoalveolar lavage (BAL) specimens, using the Allplex Respiratory Panel 1/2/3 and the Allplex SARS-CoV-2 assay as reference methods validated for both matrices. Overall, 132 BAL samples were analyzed. BioFire identified more positives than Allplex, particularly for human rhinovirus/enterovirus (HRV/EV), human parainfluenza virus (HPIV), and non–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The overall agreement was fair (κ = 0.237), and pathogen-specific concordance was almost perfect for SARS-CoV-2 (κ = 0.841), influenza A/B (κ = 0.808), and HPIV (κ = 0.884). The Panther assay showed substantial agreement with Allplex (κ = 0.719) and near-perfect concordance for SARS-CoV-2 and influenza viruses, while BioFire and Panther exhibited almost perfect interassay agreement (κ = 0.903). These findings demonstrate that assays validated for URT specimens can perform reliably on BAL samples, underlining the diagnostic potential of LRT matrices and the need for expanded validation of molecular respiratory panels across specimen types.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"28 7","pages":"Pages 517-523"},"PeriodicalIF":3.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Pathologic and Genetic Investigation of Four Young Adults with a Short QT Interval and Sudden Unexpected Death","authors":"Yukiko Hata,&nbsp;Yoshiaki Yamaguchi,&nbsp;Keiichi Hirono,&nbsp;Shojiro Ichimata,&nbsp;Koichi Mizumaki,&nbsp;Naoki Nishida","doi":"10.1016/j.jmoldx.2026.04.004","DOIUrl":"10.1016/j.jmoldx.2026.04.004","url":null,"abstract":"<div><div>Although structural heart abnormalities are not typically associated with short QT syndrome (SQTS)-related sudden unexpected death, few autopsy studies have examined the underlying pathology and genetic factors of SQTS. Therefore, comprehensive pathologic examinations and whole-exome sequencing were conducted in four men (aged 24, 28, 31, and 45 years) with sudden unexpected death and a short QT interval (sQT). No variants were identified in genes currently known to be associated with SQTS. An enrichment analysis was performed to identify potential genetic causes and mechanisms. None of the men had a history of cardiovascular disease, familial sudden death, or arrhythmia. Rare variants in <em>SCN10A, ANK2, KCNQ2,</em> and <em>CACNA1H</em> were detected, potentially associated with cardiac electrophysiology. One case exhibited apical hypertrophic cardiomyopathy with a rare <em>PLEC</em> variant. The other three displayed left ventricular hypertrabeculation with poor compaction, deep recess formation, myocardial fibrosis, micronecrosis, and minimal inflammatory cell infiltration. The enrichment analysis indicated that these variants were associated with cardiac electrophysiology and morphogenesis. These results showed that individuals with sQT may be at risk of sudden death even without a clinical or family history. This risk may be increased by cardiomyopathy-related gene variants in preclinical or early disease stages. Electrocardiographic evaluation to identify sQT cases followed by morphologic and genetic evaluations improves the assessment of a sudden death risk in individuals with sQT.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"28 7","pages":"Pages 565-574"},"PeriodicalIF":3.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical-Grade Somatic Variant Interpretation Performance via a Rule-Constrained Large Language Model Framework (Oncology Logic-Informed Variant Evaluator)","authors":"Melissa Y. Tjota,&nbsp;Peng Wang,&nbsp;Sisi Qin,&nbsp;Ming Gao,&nbsp;Wenjun Kang,&nbsp;Viswateja Nelakuditi,&nbsp;Jeremy P. Segal","doi":"10.1016/j.jmoldx.2026.04.001","DOIUrl":"10.1016/j.jmoldx.2026.04.001","url":null,"abstract":"<div><div>Interpretation of somatic variants in clinical oncology requires integration of gene-specific biology, tumor context, and multiple evidence sources. Although large language models (LLMs) can assist variant interpretation, concerns remain regarding reproducibility, safety, and dependence on opaque model behavior. A rule-constrained LLM-based decision support framework, Oncology Logic-Informed Variant Evaluator (OLIVE), was developed and evaluated for somatic variant interpretation in a clinical molecular pathology service. OLIVE summarizes multiple data sources and applies explicit gene-specific guidance files to generate structured prompts for final classification and interpretation. Performance was assessed on 200 consecutive clinical tumor next-generation sequencing cases comprising 1437 variant observations (1228 unique variants). Concordance with historical laboratory classifications was evaluated for reportable (pathogenic/likely pathogenic) versus variant of uncertain significance determinations. Across three replicates, mean concordance with historical interpretation was 97.5% (range, 97.4% to 97.6%). Forty-two variants (2.9%) showed discordance in at least one replicate, with most discordances being consistent across runs. Blinded <em>post hoc</em> expert adjudication of discordant variants demonstrated interpretive variability favoring the laboratory or OLIVE classification in equal proportions (21 versus 21 variants). Discordances predominantly reflected intrinsic interpretive ambiguity, evidence evolution, and rule stringency rather than model instability. Similar results with a different LLM indicate performance is not model dependent and is primarily driven by expert guidance. These results indicate that OLIVE can reproducibly support expert somatic variant interpretation in a real-world clinical setting.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"28 7","pages":"Pages 524-534"},"PeriodicalIF":3.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147787116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of MyHPVscore","authors":"Jordan Currie ,&nbsp;Heather Walline ,&nbsp;Colleen G. Hochfelder ,&nbsp;Chandan Bhambhani ,&nbsp;Collin V. Brummel ,&nbsp;Erin Sandford ,&nbsp;Apurva Bhangale ,&nbsp;Rawan Akhdar ,&nbsp;Marisa Buchakjian ,&nbsp;Keith A. Casper ,&nbsp;Steven B. Chinn ,&nbsp;David Forner ,&nbsp;Kelly M. Malloy ,&nbsp;Jennifer L. Shah ,&nbsp;Andrew G. Shuman ,&nbsp;Chaz L. Stucken ,&nbsp;Matthew E. Spector ,&nbsp;Francis P. Worden ,&nbsp;Pratyusha Yalamanchi ,&nbsp;Molly Heft Neal ,&nbsp;J. Chad Brenner","doi":"10.1016/j.jmoldx.2026.04.003","DOIUrl":"10.1016/j.jmoldx.2026.04.003","url":null,"abstract":"<div><div>As rates of human papillomavirus-positive (HPV⁺) oropharynx cancer increase, there is increasing need for accurate biomarkers for diagnosis, treatment, and surveillance. The analytical performance of MyHPVscore, a droplet digital PCR laboratory-developed test, was characterized to detect circulating tumor DNA from multiple high-risk HPV (hrHPV) types (16, 18, 31, 33, 35, and 39) in plasma from patients with HPV⁺cancer. Using Clinical and Laboratory Standards Institute guidelines, MyHPVscore was developed and validated in a Clinical Laboratory Improvement Amendments–certified laboratory. Analytical controls and plasma samples from patients with HPV⁺oropharyngeal squamous cell carcinoma and noncancer controls were used to evaluate sensitivity, specificity, linearity, and analyte stability. MyHPVscore demonstrated high analytical performance for detecting multiple hrHPV types. Limits of blank were 2.7 (HPV16) and 2.6 (other hrHPV types) positive droplets/reaction; limits of detection were 15.2 and 20.8 positive droplets/reaction, respectively. The linear range was 15 to 62,500 targets/mL plasma (HPV16) and 12 to 100,000 targets/mL (other hrHPV types) with strong correlation (<em>R</em>² &gt; 0.99). Analytes were stable for 96 hours at –20°C and yielded consistent qualitative results after &gt;400 days of storage. No cross-reactivity was observed between hrHPV types or low-risk types (HPV6 and HPV11). These results support the use of MyHPVscore as a laboratory-developed test for detecting HPV⁺oropharynx cancer. This method establishes an approach and standard controls that can benchmark other emerging circulating tumor DNA assays.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"28 7","pages":"Pages 553-564"},"PeriodicalIF":3.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstracts of the AMP Europe 2026 Congress","authors":"","doi":"10.1016/j.jmoldx.2026.05.001","DOIUrl":"10.1016/j.jmoldx.2026.05.001","url":null,"abstract":"","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"28 6","pages":"Pages S1-S56"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148153815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncogenicity Variant Interpreter (OncoVI) Supports Harmonized Somatic Variant Interpretation in Precision Oncology","authors":"Maria Giulia Carta ,&nbsp;Lars Tögel ,&nbsp;Annett Hölsken ,&nbsp;Christoph Schubart ,&nbsp;Heinrich Sticht ,&nbsp;Robert Stöhr ,&nbsp;Silvia Spoerl ,&nbsp;Norbert Meidenbauer ,&nbsp;Arndt Hartmann ,&nbsp;Paolo Magni ,&nbsp;Florian Haller ,&nbsp;Fulvia Ferrazzi","doi":"10.1016/j.jmoldx.2026.03.004","DOIUrl":"10.1016/j.jmoldx.2026.03.004","url":null,"abstract":"<div><div>Accurate and reproducible interpretation of somatic variants is fundamental for therapy decision-making in patients with cancer. To harmonize and automate oncogenicity classification, Oncogenicity Variant Interpreter (OncoVI), an open-source, Python-based implementation of the Clinical Genome Resource/Cancer Genomics Consortium/Variant Interpretation for Cancer Consortium oncogenicity guidelines, was developed. For each of the guideline criteria, the textual descriptions were interpreted, and publicly available resources were identified to be used as reference. Starting from the genomic coordinates of a variant, OncoVI automatically performs functional annotation, collects relevant evidence from the integrated resources, evaluates each criterion, and provides a final oncogenicity classification. OncoVI achieved an accuracy of 80% on a gold standard set of 93 somatic variants provided by the guidelines, with a sensitivity of 88% for oncogenic/likely oncogenic variants. When applied to a real-world set of 7802 variants from 557 participants previously evaluated by the Molecular Tumor Board (MTB) Erlangen, OncoVI showed 79% concordance with the prior MTB assessment of variant impact on protein function. In addition, expert reassessment of 135 MTB variants, conducted in accordance with the oncogenicity guidelines, further confirmed both the validity of OncoVI implementation and the appropriateness of the identified resources. Taken together, OncoVI provides significant support for the harmonized and reproducible oncogenicity classification of somatic variants across institutions.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"28 6","pages":"Pages 469-484"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147624641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance Evaluation of a PCR/Nanopore Assay for Carrier Screening for Cystic Fibrosis, Spinal Muscular Atrophy, and Fragile X Syndrome","authors":"Kendall E. Martin,&nbsp;Fernanda Sábato,&nbsp;Jesse Lynch,&nbsp;Andrea Ferreira-Gonzalez,&nbsp;Elizabeth S. Barrie","doi":"10.1016/j.jmoldx.2026.03.003","DOIUrl":"10.1016/j.jmoldx.2026.03.003","url":null,"abstract":"<div><div>Cystic fibrosis, spinal muscular atrophy, and fragile X syndrome are among the most common inherited genetic disorders, making carrier screening essential for identifying at-risk couples. Traditional screening often involves multiple workflows and may miss rare variants. Comprehensive sequencing offers broader variant detection across diverse populations. This study validated a PCR/Nanopore-based assay for comprehensive assessment of <em>CFTR</em>, <em>SMN1/2</em>, and <em>FMR1</em>. Samples included anonymized DNA from: whole blood (archival clinical samples; <em>n</em> = 53), cell lines (<em>n</em> = 19), and residual College of American Pathology proficiency testing material (<em>n</em> = 3). Using the AmplideX Nanopore Carrier Plus reagents, gene-specific PCR was performed, followed by barcoding and sequencing on MinION flow cells. Data were analyzed using the AmplideX One Reporter software. Results for <em>SMN1/2</em> and <em>FMR1</em> showed 100% concordance with orthogonal methods (PCR/fragment analysis laboratory-developed tests) and 97% for <em>CFTR</em>. These results were reproducible between interrun and intrarun repeats. Here, it is shown that the PCR/Nanopore-based assay is accurate and reproducible for identifying pathogenic variants and poly-T size in <em>CFTR</em>; <em>SMN1/2</em> copy number and single-nucleotide polymorphism detection; and <em>FMR1</em> CGG repeat sizes and AGG interruptions. The assay was also able to detect mosaicism as low as 10% for <em>FMR1</em>. This single workflow enables accurate, reproducible screening for multiple disorders, with the ability to identify more <em>CFTR</em> variants than traditional genotyping panels.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"28 6","pages":"Pages 485-492"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of a Low-Volume (100 μL) Plasma Protocol for HIV-1 RNA Quantification Using the Hologic Aptima HIV-1 Quant Dx Assay","authors":"Lorna S. Madurai ,&nbsp;Kiveshan Reddy ,&nbsp;Someshni Nair ,&nbsp;Bhavani Manivannan ,&nbsp;Kayla Pillay ,&nbsp;Sharana Mahomed","doi":"10.1016/j.jmoldx.2026.03.006","DOIUrl":"10.1016/j.jmoldx.2026.03.006","url":null,"abstract":"<div><div>Pediatric HIV-1 viral load monitoring is often limited by the small blood volumes that can be safely obtained from infants and young children. Standard assays typically require 0.5 to 0.7 mL of plasma, which can pose challenges in these settings. This study evaluated a modified low-volume protocol using 100 μL of plasma, diluted for use with the Hologic Aptima HIV-1 Quant Dx assay, to determine whether performance was equivalent to the standard 700 μL protocol. An analytical validation was conducted by using de-identified EDTA plasma samples spanning a wide range of HIV-1 RNA concentrations. Each specimen was tested by using both protocols on the Panther system. Agreement between methods was assessed by using log₁₀ differences, correlation analysis, and Bland-Altman analysis; within-run and between-run precision was evaluated by using replicate testing of negative, low-positive, and high-positive samples. The 100 μL protocol displayed excellent concordance with the standard method, with a mean log₁₀ difference of approximately 0.00 and a maximum difference of 0.12 log₁₀ copies/mL. No false-positive or false-negative results were observed among 30 fully suppressed samples. Precision analyses showed minimal variability, with all results within predefined acceptability criteria. These findings indicate that the low-volume Aptima protocol provides accurate and reliable HIV-1 RNA quantification and can expand access to viral load testing in pediatric patients and other clinical settings in which plasma volume is limited.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"28 6","pages":"Pages 461-468"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147624590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Impact of ClinGen Variant Curation Expert Panel Criteria Specifications on Variant Interpretation across Multiple Genes","authors":"Dina Marek-Yagel ,&nbsp;Rotem Greenberg ,&nbsp;Michal Naftali ,&nbsp;Shay Ben-Shachar ,&nbsp;Ofer Isakov","doi":"10.1016/j.jmoldx.2026.03.007","DOIUrl":"10.1016/j.jmoldx.2026.03.007","url":null,"abstract":"<div><div>Gene-specific variant interpretation guidelines are constantly being published to refine variant classification. The development, implementation, and benefit of such guidelines require careful assessment. This study evaluates the utility of these guidelines on variant interpretation. All actionable genes listed in American College of Medical Genetics and Genomics-Secondary findings version 3.3 genes with available Clinical Genome Resource (ClinGen) Variant Curation Expert Panel criteria specifications were analyzed. A total of 1223 variants in these genes were classified using the American College of Medical Genetics and Genomics/Association for Molecular Pathology criteria and revised according to the Variant Curation Expert Panel specifications. Reclassification outcomes were compared using high-confidence variants. Application of the revised guidelines resulted in score changes in 63.1% of variants, although most did not cross classification thresholds. Reclassification occurred in 20.3% of cases, predominantly as downgrades and improved concordance with ClinVar by 5.8%, particularly for benign classifications. Of 622 variants of uncertain significance (VUSs), 25.1% were resolved, with the highest resolution rates in <em>BRCA1</em>, <em>BRCA2</em>, and <em>PALB2</em>, whereas <em>LDLR</em> and <em>TPM1</em> remained largely unchanged. No consistent correlation was found between the extent of criteria modification for each guideline and VUS resolution. The utility of the guidelines was shown to be variable and gene dependent. Although most reduced VUS rates and refined benign classifications, in some, only a minor impact was achieved, suggesting standardization and calibration of future guidelines are necessary.</div></div>","PeriodicalId":50128,"journal":{"name":"Journal of Molecular Diagnostics","volume":"28 6","pages":"Pages 493-503"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147718866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}