MSeqDR mtDNA Tool set (mvTool), a one-stop mtDNA variant annotation and analysis Web service. mvTool is built upon the MSeqDR infrastructure (https://mseqdr.org), with contributions of expert curated data from MITOMAP (http://www.mitomap.org) and HmtDB (http://www.hmtdb.uniba.it/hmdb). mvTool supports all mtDNA nomenclatures, converts variants to standard rCRS- and HGVS-based nomenclatures, and annotates ab initio mtDNA variants. Besides generic annotations from dbNSFP and Variant Effect Predictor (VEP), mvTool provides allele frequencies in more than 47,000 germline mito-genomes, and disease and pathogenicity classifications from MSeqDR, Mitomap, HmtDB and ClinVar. mvTools also provides mtDNA somatic variants annotations. ‘mvTool API’ is implemented for programmatic access using inputs in VCF, HGVS, or classical mtDNA variant nomenclatures. The results are reported as hyperlinked html tables, JSON, Excel and VCF formats. MSeqDR mvTool is freely accessible at https://mseqdr.org/mvtool.php.
Input mtDNA Variants in Any of the 7 Formats Below, Mixed Formats Input is Supported:
1. Classical I: used in literature, PhyloTree, Haplogrep, 8527, 8993G, 8993d, 5787_5789d, 1494.1T, 7472.XA
2. Classical II: T8993G
3. HGVS Committee: NC_012920.1:m.8993T>G, reference version is required. This is the recommended format, being required by journals and NCBI/ClinVar. The short naming like m.8993T>G is also widely used in literature, assuming rCRS as reference.
4. VCF-style input: Tab-delimited, with at least the first 5 columns in vcf format
5. Ensembl: MT:g.8993T>G
6. Mutalyzer: NC_012920.1:g.8993T>G
7. Potential non-standard: 8527A>G
mvTool supports the chromosome names as any of the following:
chrM, chM, chrMT, chMT, M, MT, NC_012920.1.
The mvTool universal variant converter can convert the various combinations of these formats into a standard variant list in the rCRS-based HGVS (1-3) formats.
The current mtDNA variant data is mostly based on the default revised Cambridge sequence (rCRS, accession number NC_012920.1), but some commercial SNP array platforms used YRI (Yoruban, accession number AF347015) reference. mvTool can convert YRI-based positions into rCRS-based positions.