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Introduction

The Human Variome Project Consortium believes that the free and open sharing of human genetic variation information will lead to improved health outcomes for all people worldwide. We also believe that the most efficient and effective means for sharing this information is via a network of gene/disease specific databases, as described by the Project’s Global Collection Architecture.

To ensure the fullest dissemination of variation information to the genetics community, we believe that all sequence variants reported in journal articles should not only be fully and accurately described within the articles that report them, but also deposited into the appropriate gene/disease specific databases prior to publication.

We acknowledged that some journals already share these values but the adoption and implementation of appropriate guidelines for manuscript authors is patchy, especially with respect to the submission of data to databases. The Human Variome Project Consortium strongly encourages all journal editors to enforce a strict, mandatory policy that all variants be correctly described and deposited into variant databases prior to publication. Such a policy is already enforced by Human Mutation and other journals represented in the Human Variome Project’s Journal Editors Interest Group, and appears to be working effectively.

This Statement lays out the ideal scope of such a policy. We do, however, recognise that some journals will be unable to impose all aspects of this statement.

Sequence Variant Description

All manuscripts must include HUGO Gene Nomenclature Committee (HGNC) approved gene symbols (http://www.genenames.org) for the genes for which variant data are presented. If appropriate symbols do not exist, they should be obtained from the HGNC prior to submission. Commonly used alternative gene aliases may also be reported, but must not be used alone in place of the HGNC symbol.

Variants should be described using the Human Genome Variation Society (HGVS) nomenclature (den Dunnen and Antonarakis, 2000 Hum Mutat 15: 7–12). The most current guidelines are summarized on the Mutation Nomenclature Homepage at the HGVS website ( http://www.hgvs.org/mutnomen/). Examples of acceptable nomenclature are provided on that site and the rationale for insisting on the use of the nomenclature has been clearly stated (den Dunnen and Paalman, 2003 Hum Mutat 22: 181–182). An update to the mutation nomenclature was recently published regarding complex rearrangements (Taschner and den Dunnen, 2011: Hum Mutat 32: 507–511).

Important considerations include:

• Authors should check sequence variant descriptions using an automated tool, such as the Mutalyzer program (Wildeman et al., 2008 Hum Mutat 29: 6–13; http://www.LOVD.nl/mutalyzer/).
• Curated genomic reference sequences (Locus Reference Genomic or GenBank RefSeqGene) should be used where available.
• Accession numbers of reference sequences including the version number where relevant (e.g. LRG_1 or NG_007400.1) should be stated in the Materials and Methods section and as a footnote in tables listing variants.
• Variants should be defined in the text and tables using both DNA- and protein-level descriptions whenever appropriate.
• If alternative nomenclature schemes are commonly found in the literature, they may be used in addition to HGVS nomenclature, but they must be defined clearly.
• Variants may be described using dbSNP identifiers (e.g. rs123456:A>G).

1. Authors must submit all variants included in an article to the relevant gene/disease specific database prior to the manuscript being accepted for publication. Catalogues of relevant databases can be obtained from the Human Genome Variation Society web site (http://www.hgvs.org/dblist/dblist.html) and the GEN2PHEN web site (http://www.gen2phen.org/data/lsdb).
2. Journals should clearly state in their author instructions that prior submission of data to a database is no bar to acceptance of a submitted manuscript.

Important considerations include:

• Authors should confirm the status of database submission in their cover letter.
• Authors should note in the manuscript (e.g. in the Materials and Methods section) the databases to which they have submitted their variants and provide the URL(s).
• Where more than one LSDB exists for a given gene, the authors may choose which database to submit their variant data to. Factors influencing the choice might include the number of entries already in the database, evidence that the database is being actively curated, and whether the database complies with published Human Variome Project Standards and Guidelines and other published recommendations (e.g. Vihinen et al., 2012: Hum Mutat 33: 298-305)