CentoMD

CentoMD provides a curated genotype-phenotype database for interpretation and clinical evaluation of genetic variants in rare diseases.

Key Features:

• Independently curated repository: An independently curated database using stringent high-quality criteria for data inclusion that documents over 100,000 genetically screened individuals and more than 470 million variant detections.
• HPO-based clinical integration: Integration of human phenotype ontology (HPO)-based clinical data from consented patients and probands to support precise genotype-phenotype correlations.
• Variant classification and reclassification: Capacity to classify and reclassify genetic variants based on internal evidence, with reported reclassification of ~3% of previously reported variants associated with specific rare diseases.
• Automated follow-up and updates: An automated follow-up system that alerts to changes in variant classification to maintain current evidence on variant status.
• Clinical validity and causality summaries: Detailed summaries of clinical validity and causality linking detected gene variants to phenotypic associations to support interpretation.
• Quality management: Operates under a CLIA/CAP-accredited quality management system.
• Variant relevance metrics: Repository annotations indicating that approximately 57% of variant detections are clinically relevant or of uncertain significance, including a substantial portion of novel variants.

Scientific Applications:

• Variant interpretation and diagnostics: Supports evaluation and classification of genetic variants to improve accuracy of genetic diagnoses and clinical decision-making.
• Genotype-phenotype correlation: Uses HPO-linked clinical data to correlate genetic findings with specific phenotypes for diagnostic and research investigations.
• Gene discovery and research: Enables identification of novel disease genes by correlating novel genetic variants with well-defined phenotypes.
• Evidence surveillance: Provides ongoing surveillance of variant classifications to update clinical and research interpretations as evidence changes.

Methodology:

Independent curation using stringent inclusion criteria; integration of HPO-based clinical data from consented patients and probands; automated follow-up for classification changes; reclassification of variants based on internal evidence within a CLIA/CAP-accredited quality management framework.