HGVS nomenclature

HGVS nomenclature
Name	HGVS nomenclature
Established	2000s
Discipline	Molecular genetics
Location	International

HGVS nomenclature is the standardized system for describing variants in DNA, RNA, and protein sequences, developed to enable clear communication among clinicians, researchers, and database curators. It complements sequence databases and reporting frameworks used by organizations such as the World Health Organization, European Molecular Biology Laboratory, National Institutes of Health, American College of Medical Genetics and Genomics, and International Organization for Standardization. The nomenclature interfaces with resources like Ensembl, GenBank, UniProt, ClinVar, and dbSNP to ensure reproducible variant identification across platforms.

Overview

HGVS nomenclature arose from collaborative efforts involving stakeholders such as the Human Genome Organisation, Human Variome Project, Genetics Society of America, European Society of Human Genetics, and standards bodies including the International Nucleotide Sequence Database Collaboration. Influential contributors and working groups have included researchers affiliated with institutions like Cold Spring Harbor Laboratory, Wellcome Sanger Institute, Broad Institute, Max Planck Institute for Molecular Genetics, and Institut Pasteur. The system sits alongside related conventions used by projects such as the 1000 Genomes Project, ENCODE Project, UK Biobank, Exome Aggregation Consortium, and clinical initiatives such as Matchmaker Exchange.

Nomenclature Principles and Syntax

HGVS nomenclature specifies a concise syntax for variant descriptions, aligning with practices promoted by bodies like the International Committee on Medical Journal Editors, American Society of Human Genetics, European Molecular Genetics Quality Network, and College of American Pathologists. The syntax encodes sequence type prefixes (e.g., g., c., r., p.), coordinates, and variant types using standardized operators and delimiters adopted in variant reporting by journals such as Nature Genetics, The New England Journal of Medicine, and The Lancet. Community coordination involves repositories and projects including ClinGen, Global Alliance for Genomics and Health, GA4GH, and initiatives led by institutions like Johns Hopkins University and Stanford University.

Sequence Types and Reference Sequences

HGVS distinguishes reference sequence types that are maintained in databases run by organizations such as National Center for Biotechnology Information, European Bioinformatics Institute, UniProt Consortium, RefSeq, and Ensembl Genomes. Reference sequence selection interacts with standards and resources from Genome Reference Consortium, Human Genome Project, Haplotype Reference Consortium, and population databases like gnomAD, HapMap, 1000 Genomes Project, and UK Biobank. Use of transcript and protein references invokes identifiers curated by groups at National Human Genome Research Institute, Sanger Centre, and commercial entities including Illumina and Thermo Fisher Scientific when generating clinical reports.

Mutation Classes and Examples

HGVS classifies variant classes such as substitutions, deletions, insertions, duplications, indels, and complex rearrangements; these categories are used by clinical laboratories associated with institutions like Mayo Clinic, Cleveland Clinic, Mount Sinai Health System, and research centers such as Massachusetts General Hospital, Dana-Farber Cancer Institute, MD Anderson Cancer Center, and Memorial Sloan Kettering Cancer Center. Examples in the literature often appear in case reports and databases curated by ClinVar, HGMD, COSMIC, dbVar, and institutional registries maintained by entities including Dana-Farber, St Jude Children's Research Hospital, and Children's Hospital of Philadelphia. Variant annotation examples are integrated into pipelines developed at Broad Institute, EMBL-EBI, Stanford Center for Genomics and Personalized Medicine, and commercial platforms by Sophia Genetics and F. Hoffmann-La Roche.

Use in Clinical and Research Settings

HGVS descriptions are incorporated into diagnostic reports and registries overseen by regulatory and professional organizations such as the Food and Drug Administration, European Medicines Agency, British Society for Genetic Medicine, Clinical Laboratory Improvement Amendments, College of American Pathologists, and American Medical Association. Clinical variant interpretation workflows link HGVS terms with classification frameworks like those from ACMG, AMP, ClinGen, and specialized consortia such as InSiGHT and ENIGMA. Research consortia and projects that standardize variant reporting include Cancer Genome Atlas, ICGC, Pediatric Cancer Genome Project, H3Africa, and initiatives at universities such as Yale University, University of Cambridge, Harvard University, University of Oxford, and Princeton University.

Tools, Resources, and Implementation Considerations

Parsing, canonicalization, and conversion tools that support HGVS are developed by organizations and projects including Mutalyzer, Variant Effect Predictor, SnpEff, ANNOVAR, VEP, Ensembl, NCBI, UCSC Genome Browser, and commercial vendors such as PerkinElmer and QIAGEN. Integration into laboratory information systems and electronic health records engages platforms and standards maintained by Epic Systems Corporation, Cerner Corporation, HL7 International, FHIR, and initiatives led by National Institutes of Health. Training materials, workshops, and guidelines are disseminated through conferences and societies including American College of Medical Genetics and Genomics Annual Clinical Genetics Meeting, European Human Genetics Conference, ASHG Annual Meeting, and publisher platforms like Wiley-Blackwell and Springer Nature.

Category:Genetics