MSeqDR News and Progress in Genomic Discovery in Mitochondrial Disease

  •  January 1, 2021 MSeqDR is migrated to a new webserver at CHLA
  •  October 20, 2020 International Research Team Develops Consensus Variant Classification Guidelines for Genomic Variants in Mitochondrial DNA
  •  August 24, 2020 mvTool v.5: New report layout and new mtDNA variant data from 200,000 healthy people
  •  July 2, 2020 Recent publications from MSeqDR supported by the UMDF and NIH grants
  •   ClinGen / ClinVar – MSeqDR Working Groups & Expert Panels
  •  June 30, 2020 ClinGen approved the MSeqDR Consortium mitochondrial DNA Sequence Variant Interpretation (SVI) specifications
  •  April 29, 2020 U24 Mitochondrial Diseases Expert Panel is establishing 63 genes’ Leigh Disease associations at ClinGen
  •  January 27, 2020 MSeqDr joins FAIRsharing – A curated resource on data and metadata standards
  •  January 2, 2020 Quick-Mitome version 2 with new annotations, workflow, and tutorial
  •  October 1, 2019 Mondo Disease Ontology is coming to MSeqDR, Disease Portal received more disease entries
  •  June 12, 2019 MSeqDR to present tutorial workshop for the 5th year at the UMDF Mitochondrial Medicine Symposium
  •  May 23, 2019 mvTool v3: Added variant data from 40,000 people, Asians and Sadinians, meta-AF reference, new single variant report
  •  January 31, 2019 Leigh Syndrome Resources at
  •  November 16, 2018 MSeqDR’s ClinVar style variant submission system supports ClinVar template v4.2 (2018.08)
  •  October 17, 2018 MSeqDR mvTool Documentation
  •  September 24, 2018 Quick-Mitome is updated with Exomiser V10.1, ID de-identification, WES and WGS data support
  •  August 2, 2018 ClinVar style variant submission and curation system version 2 is released
  •  July 30, 2018 The “Mitochondrial Disease Variant Curation Expert Panel” by MSeqDR Consortium
  •   The “Mitochondrial Disease Gene Curation Expert Panel” by MSeqDR Consortium
  •  July 13, 2018 MSeqDR presented the 4th year tutorial workshop, at the UMDF Mitochondrial Medicine Symposium
  •  July 1, 2018 MSeqDR has Tripled the LSDB Variants to 11,800 since UMDF 2017
  •  May 2, 2018 New publications on clinical review of mitochondrial disease, in Current Genetic Medicine Reports
  •  March 27, 2018 New MSeqDR publication: MSeqDR mvTool: A mitochondrial DNA web and API resource
  •  February 7, 2018 New tool set: Quick-Mitome – Phenotype-Guided WES and WGS Variant Interpretation
  •   Tool update: mvTool V.2 – mtDNA variant annotation and analysis web-service with API
  •  February 5, 2018 Invitation: Join MSeqDR – UMDF Workshop, 06/30/2018 at Mitochondrial Medicine 2018
  •   Mitochondrial biology conferences 2018
  •  September 25, 2017 MSeqDR Gene Panel Examiner and Universal Gene ID Mapper
  •   mvTool V2 – Universal mtDNA Variant Converter and One Stop Annotation
  •  May 17, 2017 mvTools is updated to latest version of MitoMaps, HmtDB and ClinVar Data
  •  February 13, 2017 MSeqDR Admin, Curation, Development Roadmap
  •  February 10, 2017 MSeqDR mtDNA Expert Panel Members Added to MSeqDR
  •  January 22, 2017 MSeqDR mtDNA Expert Panel Members
  •  December 13, 2016 MSeqDR Clinical Tool Portal
  •   MSeqDr Project and Dr. Marni Falk are reported in current issue of the CHOP Bench to Bedside monthly online newsletter
  •   Expert Panel Recruiting
  •   New tool set: Phenotype-Guided Exome Prioritization with HPO and Exomiser
  •   MSeqDR – UMDF Workshop, as the concluding program of Mitochondrial Medicine 2016
  •   New MSeqDR Publication in Human Mutation
  •   New MSeqDR Publication
  •   CSH Molecular Case Studies Designates MSeqDR for Manuscript Variant Submission
  •   MSeqDR-Genesis and Dr. Marni Falk are featured in the 2015 CHOP Annual Report
  •  December 10, 2016 MSeqDR News
    2018-05-02: MSeqDR is switched to a news system based on **MSeqDR Wordpress**.
    You are welcome to publish updates related to the MSeqDr Consortium and mitochondrial diseases.



    • Tool update: MSeqDR mvTool Version 2.0: mtDNA variant annotation and analysis web-service with API.

      Input mtDNA variants in any of the 7 major formats, mixed formats input is supported. The results are returned as multiple html tables, as well as a downloadable combined Excel file. An API is implemented, which takes inputs in VCF, HGVS, or classical mtDNA variant nomenclatures, and returns annotated vcf or json outputs.


    • Tool update: Gene Panel Examiner V2: MSeqDr Gene Panel Examiner and Universal Gene ID Mapper.

      Input HGNC Approved Gene Symbols, Refseq Gene Symbols, Entrez Gene IDs, Ensembl Gene IDs, Refseq Accession, OMIM, UniProt, CCDS, VEGA, or UCSC IDs.

    • New grant: MSeqDR U24 proposal to perform expert disease-gene and gene-variant curation for Leigh syndrome is approved for funding.

    Tool update: MSeqDR mvTool Version 2.0: mtDNA variant annotation and analysis web-service with API
    • VariantOneStop is updated with dbNSFP v3.4, notably added CADD, M-CAP and REVEL scores, ExAC and 1000Gp3 population allele frequencies, conservation scores enhanced to 100way.
      VariantOneStop is updated with population frequency data from Genome Aggregation Database (gnomAD), The data set spans 123,136 exomes and 15,496 genomes from unrelated individuals sequenced as part of various disease-specific and population genetic studies.

    • MSeqDR HPO Browser is enhanced to always show 5 levels in ontology tree, HPO database is updated to 201701 release.

      HPO Browser is enhanced to always show 5 levels in tree, rather than the previous 3 levels: Grandparent, parent, self, child, grand child. Terms are shown with full HPO name in grand child.

      HPO update to 201701 release is getting significantly more genes for some HPO terms, presumably resulting from increased phenotype-gene-disease association data in HPO data release
    • More mtDNA Exomes (218) in M1 Exome dataset with mtDNA variants increased from 1316 to 1534.

    2016-12-01 2016-09-25
    • Expert Panel Recruiting: MSeqDr is organizing an expert panel for mitochondrial diseases and pathogenic variants. Welcome to share your expertise. Please visit the site to see current panel members, tools and documents.
    2016-09-25 2016-09-25 2016-09-25 2016-06-18 2016-06-18 2016-05-12
    • New Publication:

      MSeqDR: A Centralized Knowledge Repository and Bioinformatics Web Resource to Facilitate Genomic Investigations in Mitochondrial Disease Hum Mutat. 2016 Jun;37(6):540-8. doi: 10.1002/humu.22974. Epub 2016 Mar 21., Pubmed 26919060


      MSeqDR is the Mitochondrial Disease Sequence Data Resource, a centralized and comprehensive genome and phenome bioinformatics resource built by the mitochondrial disease community to facilitate clinical diagnosis and research investigations of individual patient phenotypes, genomes, genes, and variants. A central Web portal ( integrates community knowledge from expert-curated databases with genomic and phenotype data shared by clinicians and researchers. MSeqDR also functions as a centralized application server for Web-based tools to analyze data across both mitochondrial and nuclear DNA, including investigator-driven whole exome or genome dataset analyses through MSeqDR-Genesis. MSeqDR-GBrowse genome browser supports interactive genomic data exploration and visualization with custom tracks relevant to mtDNA variation and mitochondrial disease. MSeqDR-LSDB is a locus-specific database that currently manages 178 mitochondrial diseases, 1,363 genes associated with mitochondrial biology or disease, and 3,711 pathogenic variants in those genes. MSeqDR Disease Portal allows hierarchical tree-style disease exploration to evaluate their unique descriptions, phenotypes, and causative variants. Automated genomic data submission tools are provided that capture ClinVar compliant variant annotations. PhenoTips will be used for phenotypic data submission on deidentified patients using human phenotype ontology terminology. The development of a dynamic informed patient consent process to guide data access is underway to realize the full potential of these resources.


    • New Publication:
      COMMENTARY: From case studies to community knowledge base: MSeqDR provides a platform for the curation and genomic...the Mitochondrial Disease Sequence Data Resource (MSeqDR; ). This multidimensional data resource aims...

    • Authors: Marni J. Falk, Lishuang Shen, Xiaowu Gai
    • Cold Spring Harb Mol Case Studies May 2016, 2: a001065 Full Text, Full Text (PDF)


    • Project Update: MSeqDR and Dr. Marni Falk and the GENOMIT

      GENOMIT - Mitochondrial Disorders – Connecting Biobanks, Empowering Genetic Diagnostics and Exploring Disease Models.


    • Project Update: CSH Molecular Case Studies Designates MSeqDR for Manuscript Variant Submission. will serve as a permanent site to host the pathogenic variants associated with manuscripts to "CSH Molecular Case Studies".

      Novel disease genes and variants can be added to MSeqDR-LSDB. A custom MSeqDR accession number is assigned to all annotated pathogenic variants that are either submitted by users or batch extracted from other databases such as ClinVar or Ensembl, each containing a unique MSCV (MSeqDR Clinically-related Variant) identifier with a 7-digit code. Users can readily submit variants, in either VCF or HGVS formats, using the custom MSeqDR ‘Pathogenic variant submission tool’ (


    • Project Update: MSeqDR-Genesis and Dr. Marni Falk are featured in the 2015 CHOP Annual Report, The Children's Hospital of Philadelphia .

      It's also highlighted in the CSO's last bullet point:

      "Find out how a curious researcher contemplating a seemingly unsolvable patient case can reach out to another investigator on the opposite side of the world studying a patient with a similar genetic makeup. Working together, in a matter of minutes they can pinpoint the genetic mutations that may explain the rare disease that their patients have in common".




    • Project Update: Live Demo Workshop at SIMD'15

      The workshop achieved surprisingly high turnout and received nice feedbacks.

      Over 70 clinicians, scientists and genetic counselors, from over worldwide institutes and hospitals, registered and attended the workshop.

      Read the attendees' comments (survey)


    • Project Update: Live Demo Workshop at SIMD 2015

      The participants at the Society of Inherited Metabolic Disease (SIMD) Meeting in Salt Lake City, Utah are invited to to join us for a "FIRST-EVER" hands-on tutorial for MSeqDR/ and related matchmaker exchange tools.

      Speaker: Dr. Marni Falk, the Children's Hospital of Philadelphia

      Location: Grand America Hotel in Salt Lake City, Utah

      Time: MONDAY 3/30/15 from 12:30-2PM.

      The full address: 555 South Main Street Salt Lake City, Utah 84111.


    • Publication:
      The paper describing another tool developed by MSeqDR project is accepted for publication:

      Phy-Mer: a novel alignment-free and reference-independent mitochondrial haplogroup classifier. Bioinformatics 2014: btu825v1-btu825, Pubmed 25505086.

      Daniel Navarro-Gomez, Jeremy Leipzig, Lishuang Shen, Marie Lott, Alphons P.M. Stassen, Douglas C. Wallace, Janey L. Wiggs, Marni J. Falk, Mannis van Oven, and Xiaowu Gai

    • Project Update: Phy-Mer, MSeqDR's own haplogroup classifier tool is running as web-based service in MSeqDR. Phy-Mer is a novel alignment-free and reference-independent tool, and it supports input in fasta, fastq, bam, csv formats.
    • Project Update: LSDB is upgraded to LOVD 3.0.12, which restored the gene and variant creation funtions that rely on Mutalyzer webservice.
    • Publication:
      The first paper describing the MSeqDR Project is accepted for publication:

      Mitochondrial Disease Sequence Data Resource (MSeqDR): A global grass-roots consortium to facilitate deposition, curation, annotation, and integrated analysis of genomic data for the mitochondrial disease clinical and research communities.

      Falk MJ, Shen L, Gonzalez M, Leipzig J, Lott MT, Stassen AP, Diroma MA, Navarro-Gomez D, Yeske P, Bai R, Boles RG, Brilhante V, Ralph D, DaRe JT, Shelton R, Terry SF, Zhang Z, Copeland WC, van Oven M, Prokisch H, Wallace DC, Attimonelli M, Krotoski D, Zuchner S, Gai X.

      Mol Genet Metab. 2015 Mar;114(3):388-396. doi: 10.1016/j.ymgme.2014.11.016. Epub 2014 Dec 4. pii:S1096-7192(14)00377-1. doi: 10.1016/j.ymgme.2014.11.016., Pubmed 25542617, Draft,Fig1 Fig2A Fig2B

    2014-11-10 2014-07-24
    • Publication:

      MToolBox: a highly automated pipeline for heteroplasmy annotation and prioritization analysis of human mitochondrial variants in high-throughput sequencing. Bioinformatics. 2014 Nov 1;30(21):3115-7, Pubmed

      Calabrese C, Simone D, Diroma MA, Santorsola M, Guttà C, Gasparre G, Picardi E, Pesole G, Attimonelli M.

    • Project Update: MToolBox, Haplogroup classifier tool is running as web-based service in MSeqDR. MToolBox supports input in fasta, fastq, and bam/sam formats.
    2014-06-04 2014-05-22
    • Project Update: MitoBreak LogoMitoBreak : The major mitochondrial DNA breakpoints database, shared well-curated data for 805 mitochondrial DNA deletions and 44 duplications with pathogenic annotations. The data can be viewed as GBrowse track "MitoBreak DNA Breakpoints".
      Dr. Filipe Pereira;  Joana Damas, University of Porto, Portugal
    • Project Update: MITOMAP: A human mitochondrial genome database, shared ~10,300 manually curated polymorphisms and mutations in human mitochondrial DNA, including 580 with pathogenicity annotations. Lead by Dr. Doug Wallace, and manually curated by Marie Lott.
    • Project Update: MT.AT : Dr. Fons Stassen from Maastricht University, Netherland, Develops a new mtDNA Variant Annotation Tool for haplogroup analysis with samples, experiments and variants.
    • Project Update:

      PhyloTree Logo PhyloTree is here: 4809 haplogroups, 4228 unique haplogroup defining variants at 3940 positions

      Based on mtDNA tree Build 16 (rCRS reference) and maintained by Dr. Mannis van Oven.

      Citation: van Oven M, Kayser M. 2009. Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation. Hum Mutat 30(2):E386-E394. doi:10.1002/humu.20921

      View the full list as GBrowse Track.

    • Project Update:

      MSeqDR server is migrated to MEEI, Harvard University. A new domain name for the project: https:/ .

      Human Phenotype Ontology support is being implemented. Search by accession# or keywords at: HPO Search, and at top search box (prefix keywords with "PH:").

    • Project Update:

      Two major variation tracks are added. The were provided by HmtDB Project lead by Dr. Marcella Attimonelli. HmtDB is a Human Mitochondrial Genomic Resource Based on Variability Studies Supporting Population Genetics and Biomedical Research.

      The data are derived from a pool of 1000 healthy and about 2000 patient genomes annotated in HmtDB. The tracks have been produced according to rCRS and RSRS.

      The HBCR annotation is updated to dbSNP138.

    • Project Update:

      MSeqDR-LSDB , the Mitochondrial Disease Locus Specific Database, is open to the public. It is a major effort in promoting information integration and sharing.

      This LSDB is integrating phenotyping and variation data from multiple comprehensive or disease specific resources, including clinVar, MITOMAP, Ensembl phenotype, and OMIM. It will focus on genes involved in mitochondrial diseases, whose products are located in mitochondrian, and mitochondrial genome. The clinical, genetics, and variants information will be available. The LSDB is based on LOVD (v3.0.08) with extensive in-house customizations and enhancements.

    • Project Update: Phenotype associated variants are added as new tracks in Gbrowse, and available from our new MSeqDR-LSDB. The information were compiled from clinVar, MITOMAP , and Ensembl .
    • Project Update: HBCR: Human BP Codon Resource Variant Annotation Pipeline @ MSeqDR in online. It can handle up to 1 million variants per hour. It accepts VCF format and tabbed text format input. Please try out.


    • Project Update: We are delighted that the aggregated variantion data for NuclearMitome Comprehensive Sequence Analysis of 448 Nuclear Mitochondrial Genes from Transgenomic Inc., is available at MSeqDR. Interested users please contact the company for access request. The dataset has ~108K variants from 151 patients, targeting 448 candidate genes for mitochondrial disease.


    • Project Update: WebEx discussion between MSeqDR, MITOMAP and HmtDB on collaborating in bring together tools and data for mitochondrial research.
    • Project Update: MSeqDR monthly WEBEX meeting.
    • Project Update: MSeqDR monthly WEBEX meeting.
    • Project Update: CRAs now active with: Dr. Mark Tarnopolsky (McMaster), Drs. Richard Rodenburg and Jan Smeitink (Netherlands), Dr. Marcella Attimonelli (Italy), Dr. Michio Hirano (Columbia), Dr. Jeana DaRae and David Ralph (Transgenomic).
    • Project Update: MSeqDR server is upgraded from development server to powerful production server: 24 Intel(R) Xeon(R) CPU E5-2430 processors @ 2.20GHz, 32 GB memory.


    • Project Update: MSeqDR CHOP-Transgenomic collaborative research agreement completed.


    • Project Update: MSeqDR monthly WEBEX meeting.
    • Data Access: dbSNP137 SNPs and effect annotation, 1000 Genome variants, Hapmap variants uploaded to MSeqDR Gbrowse .
    • Data Access: Mitomap variants and disease associations, mitoCarta, GeneDX data incorporated in MSeqDR Gbrowse .


    • Data Update: HBCR annotation is completed for MSeqDR exome variants. 1010 exomes samples were included in this release.


    • Data Access: MSeqDR Gbrowse server running. MSeqDR Exome variants and annotations loaded. Ensembl human gene annotations and EVS exome data loaded.
    • Project Update: MSeqDR monthly WEBEX meeting.


    • Project Update: New MSeqDR team member Lishuang Shen started working for the development.


    • Project Update: MSeqDR project funding.


    • Project Update: MSeqDR: Mitochondrial Disease Sequence Data Resource Consortium was initiated at Annual Meeting of the United Mitochondrial Disease Foundation (UMDF).