Nomenclature for the description of sequence variations

J.T. den Dunnen, S.E. Antonarakis: Hum Genet 109(1): 121-124, 2001

Reproduced with kind permission from Prof. S. E. Antonarakis

(last modified March 7, 2001)


Questions and comments regarding nomenclature should be directed to Professor Stylianos Antonarakis ( ) or Dr. Johan T. den Dunnen ( ). This page can also be found at the HGVS site.



Recently, a nomenclature system has been suggested for the description of changes (mutations and polymorphisms) in DNA and protein sequences [Antonarakis, S.E. and the Nomenclature Working Group (1998) Recommendations for a nomenclature system for human gene mutations. Hum.Mut. 11: 1-3]. These nomenclature recommendations have now been largely accepted and stimulated the uniform and unequivocal description of sequence changes. However, current rules do not yet cover all types of mutations, nor do they cover more complex mutations. This document lists the existing recommendations and summarizes suggestions for the description of additional, more complex changes, (shown in italics) based on a manuscript published in Human Mutation [den Dunnen, JT and Antonarakis, SE (2000). Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum.Mut. 15: 7-12] (copy in PDF format).

Discussions regarding the advantages and disadvantages of the suggestions are necessary in order to continuously improve the designation of sequence changes. The consensus of the discussions will be posted here and we invite investigators to communicate with us regarding these suggestions. Furthermore, we invite investigators to send us complicated cases not covered yet, with a suggestion of how to describe these (mail to and We hope these pages will be used as a guide to describe any sequence change, ultimately evolving into a uniformly accepted reference for mutation nomenclature description.

General recommendations

(suggestions extending the current recommendations are in italtics)

The term "sequence variation" is used to prevent confusion with the terms "mutation" and "polymorphism", mutation meaning "change" in some disciplines and "disease-causing change" in others and polymorphism meaning "non disease-causing change" or "change found at a frequency of 1% or higher in the population".

The basic recommendation is to use systematic names to describe each sequence variation. For this, variations are described at the most basic level, i.e. the DNA level, using either a genomic or a cDNA reference sequence. A genomic reference sequence is preferred because it overcomes difficult cases, including multiple transcription initiation sites (promoters), alternative splicing, the use of different poly-A addition signals, multiple translation initiation sites (ATG-codons) and the occurence of length variations. When, like in most cases, the entire genomic sequence is not known, a cDNA reference sequence should be used instead.

DNA level

Description of nucleotide changes

RNA level

Sequence changes at RNA level are basically described as those at the DNA level with the following modifications/additions;

Protein level

Sequence changes at protein level are basically described as those at the DNA level with the following modifications/additions;

Description of amino acid changes

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