HmtVar is a free resource hosting variability and pathogenicity data about human mitochondrial variants; this information is also integrated with data coming from several online databases and tools focused on the mitochondrial genome.

Database content

HmtVar contains variants data coming primarily from complete human mitochondrial genomes stored in the HmtDB online resource.

HmtVar variants are gathered from variantions found in complete human mitochondrial genomes downloaded from GenBank in HmtDB and derived from individuals with apparently healthy phenotype and individuals with disease phenotypes (annotated in HmtDB as "healthy" and "pathologic" respectively). Caveat: genomes available in HmtDB also include coding-region-only sequences, whose variants are not included in HmtVar, since these genomes are not complete.

Variants are determined based on the rCRS mitochondrial reference sequence.

HmtVar offers a pathogenicity prediction for both non synonymous and tRNA variants; these predictions are calculated using variants nucleotide variability and specific pathogenicity criteria, as detailed in Santorsola et al for non-synonymous variants and in Diroma et al for tRNA variants.

tRNA variants attributes are manually curated and further information can be found on the tRNA models page.

Database structure

Each variant in HmtVar is associated to the following attributes, which allow an exhaustive data retrieval through both the Query page or the API functionalities.

Main Information

Allows to query the basic information regarding variants; these data include:

Locus type to which the variant belongs: Coding sequences (CDS), Regulatory sequences, rRNA, tRNA.
Specific mutation, in the formats
  • [ref_nt][position][alt_nt] (e.g. T3308A)
  • [ref_nt][position] (e.g. T3308)
  • [position][alt_nt] (e.g. 3308A)
Variants occurring in one or more positions in the mitochondrial genome, in the formats
  • [position] (single position)
  • [pos_1,pos_2,pos_3] (list of positions)
  • [start_pos-end_pos] (range of positions)
Variants occurring in one specific mitochondrial locus.
In case of a Coding Sequence variant, the codon position it belongs to.
In case of a Coding Sequence variant, the aminoacidic change it determines.
The variant disease score calculated by HmtVar, in the formats
  • [dis_score] (specific value)
  • [min_score-max_score] (range of disease scores)
In case of a tRNA variant, the tRNA model it belongs to.
The variant pathogenicity predicted by HmtVar: Likely Pathogenic, Likely Polymorphic, Pathogenic, Polymorphic.

Variability

Allows to query the variability information regarding variants; these data include:

The nucleotide variability of the variant in healthy individuals and patients, in the formats
  • [variab] (single value)
  • [min_var-max_var] (range of variability)
The aminoacid variability of the variant in healthy individuals and patients, in the formats
  • [variab] (single value)
  • [min_var-max_var] (range of variability)

Variant Card

After performing a query, detailed information about a specific variant is shown in a Variant Card, which gathers all the data available using different tabs. These tabs are:


Main Info

Contains variant’s basic information such as its location, the consequent amino acidic change for non-synonymous variants or specific structural details for tRNA variants, haplogroups and macro-haplogroups code if the variant is associated to a specific haplogroup according to Phylotree build 17, as well as HmtVar pathogenicity prediction.


Variability

Shows nucleotide and amino-acidic variability values, for both healthy and diseased genomes; in the same tab, healthy, diseased and continent-specific allele frequencies are also reported.


Pathogenicity Predictions

Shows a more detailed view of pathogenicity annotated in HmtVar inclusive of the global disease score, as well as pathogenicity scores calculated by the predictors used to estimate the DS value.


External Resources

Shows a set of additional variant information coming from online resources focused on diseases (Mitomap, ClinVar, OMIM), population studies (dbSNP and 1000Genomes) and structural information (Mamit-tRNA). Links to the original sources of information are always provided for consistency.


Download Data

Allows users to download each variant’s data for offline use. Data are provided in a JSON-formatted file, which contains all the information available for the variant selected.

Citing HmtVar

HmtVar can be cited using the latest publication, available on Nucleic Acids Research:

Preste R, Vitale O, Clima R, Gasparre G, Attimonelli M

HmtVar: a new resource for human mitochondrial variations and pathogenicity data.

Nucleic Acids Res. 2018 Oct 29.

Code for HmtVar can be found on the official GitHub repository, where a subset of the actual data is available to test the database and play with it.