Sequence Variant Descriptions: HGVS Nomenclature and Mutalyzer

Johan T. den Dunnen1

1 Clinical Genetics & Human Genetics, Leiden University Medical Center, on behalf of the HGVS/HVP/HUGO Sequence Variant Description Working Group (SVD‐WG), Leiden, The Netherlands
Publication Name:  Current Protocols in Human Genetics
Unit Number:  Unit 7.13
DOI:  10.1002/cphg.2
Online Posting Date:  July, 2016
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Consistent and unambiguous description of sequence variants is essential to report and exchange information on the analysis of a genome, in particular in DNA diagnostics. The HGVS nomenclature—recommendations for the description of sequence variants as originally proposed by the Human Genome Variation Society—has gradually been accepted as the international standard for variant description. In this unit, we describe the current recommendations (HGVS version 15.11) regarding how to describe variants at the DNA, RNA, and protein level. We explain the rationale and give example descriptions for all variant types: substitution, deletion, duplication, insertion, inversion, conversion, and complex, as well as special types occurring only on the RNA (splicing) or protein level (nonsense, frame shift, extension). Finally, we point users to available support tools and give examples for the use of the freely available Mutalyzer suite. An extensive version of the HGVS recommendations is available online at © 2016 by John Wiley & Sons, Inc.

Keywords: standards; nomenclature; variant; DNA; mutation; sequencing; diagnostics

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Table of Contents

  • Recommendations
  • Basic Protocol 1: Mutalyzer
  • Concluding Remarks
  • Acknowledgments
  • Figures
  • Tables
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Basic Protocol 1: Mutalyzer

  • Computer with high‐speed Internet connection
  • Web browser
  • Reference and variant sequence or variant description
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Literature Cited

Literature Cited
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Internet Resources
  HUGO Gene Nomenclature Committee (HGNC).
  Up to data Web pages for variant nomenclature recommendations.
  Posts and discussions on HGVS recommendations
  DNA Data Bank of Japan (DDBJ).
  European Bioinformatics Institute (EBI).
  National Center for Biotechnology Information (NCBI) at the U.S. National Institutes of Health.
  Locus Reference Genomic (LRG).
  NCBI reference sequences (RefSeq).
  List of all gene variant databases (Locus Specific DataBases or LSDB)s. To link to specific gene variant database based upon its HGNC‐approved gene symbol, use http://{GeneSymbol}, like or, etc.
  the Mutalyzer suite of HGVS nomenclature support tools, incl. Variant Description Extractor
  the Variant Validator of HGVS descriptions
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