The Mutalyzer sequence variation nomenclature checker is a free web-based tool that checks descriptions of sequence variations according to the international standards recommended by the Human Genome Sequence Variation Society (HGVS) (For an overview, visit http://www.hgvs.org/mutnomen/). Please see the help file for detailed information about the program.
LSDB curators are adviced to follow the LSDB recommendations of the Human Genome Sequence Variation Society (For an overview, visit http://www.hgvs.org/rec.html ). The recommendations include specification of the HGNC symbol of the gene of interest and its reference sequence.
Due to changes of the HGVS sequence variation nomenclature guidelines and their implementation in Mutalyzer, LSDB curators are also adviced to list the version of the HGVS guidelines and the Mutalyzer program used for curation of variants.
LSDB curators can provide a link to Mutalyzer on their LSDB web site allowing submitters to check new variants with Mutalyzer's Name Generator or Name Checker before submission. They can also use the program to curate existing entries. Mutalyzer's Name Generator is the tool to use when the format of the description is not already clear. Alternatively, LSDB curators can use LOVD 2.0 (Leiden Open source Variation Database) software with the Mutalyzer module, which automatically checks new submissions.
LSDB curators can convert dbSNP Reference SNP identifiers (for example rs9919552) into HGVS-compliant descriptions based on a specified reference sequence using Mutalyzer's SNP converter.
LSDB curators can check the contents of their LSDBs using Mutalyzer's Batch Checker.
Many LSDB curators are using RefSeq records (Accession number starting with NM_ or XM_) as a reference sequence. These records describe transcript sequences and cannot be used by Mutalyzer to describe intron variants. Mutalyzer 1 can use NCBI's RefSeqGene records, which are well-annotated genomic reference sequences with cross-references to other RefSeq records.
Under the auspices of the EU-funded Gen2Phen project, the NCBI and the EBI are generating new stable genomic reference sequences, the Locus Reference Genomic (LRG). Because of their stability, the use of LRGs is recommended for diagnostic labs. Requests to create new LRGs can be send to request@lrg-sequence.org. However, LRGs can only be used with Mutalyzer 2, which is currently being developed. Most LRGs are based on RefSeqGene records as described here.
Mutalyzer 1 needs the accession number of a Genbank reference sequence file to retrieve basic information from the annotation for the check. Always use an Accession number (AL449423) in combination with a specific version number (14). Otherwise, Mutalyzer automatically uses the last version and may present unexpected results.
Mutalyzer can check all variants using a well-annotated genomic reference sequence (See AL449423.14 for CDKN2A or NCBI's RefSeqGene records for example). If the transcript specified by the NM_ number is annotated in the genomic record, Mutalyzer can describe any variant relative to this transcript. In addition, it will also generate descriptions relative to other transcripts or proteins, which are annotated in the sequence record.
Therefore, LSDB curators are adviced to use a well-annotated genomic reference sequence. It is easy to obtain a suitable genomic reference sequence with Mutalyzer's GenBank Uploader by either using an HGNC symbol or a chromosomal position. We strongly recommend to limit your use of these options and to send a request for a new RefSeqGene record to rsgene@ncbi.nlm.nih.gov. LSDB curators using LOVD 2.0 can import the sequence files obtained using the Reference Sequence Parser 2.0.
If you have any comments or suggestions be sure to let us know!
Last modified: June 11, 2010
Mutalyzer@humgen.nl