Examples - 13:20763071:T>C, 13:20763044, 13:20763045-20763071

What's new?

We are very excited to announce the release of DVD v8.2! With this release, we have modified our list of genes to be consistent with the newest version of our OtoSCOPE® genetic testing platform.

Below is a list of changes we made for this release.

Version 8.2 changes

  • VEP Annotations

    Ensembl's VEP has replaced ASAP for all variant annotations. This resolves discrepancies from ASAP's atypical InDel formatting as well as providing additional information for review on gene variant lists and on variant pages.

    For more information on VEP please see Ensembl's website.

    Note: We gather SIFT and PolyPhen-2 scores from both VEP and dbNSFP. In the event that both VEP and dbNSFP provide scores for a variant, VEP's SIFT and PolyPhen-2 scores override those of dbNSFP as a factor in our variant pathogenicity classification.

  • GnomAD Information Integration:

    GnomAD 2.0 variant frequencies are now available when viewing variant information. Please note that this data does not contribute to variant pathogenicity classifications and is provided for informational purposes only. GnomAD integration into pathogenicity classification is coming soon!

  • CADD Information Integration:

    CADD phred score information is now available when viewing variant information. Please note that this data does not contribute to variant pathogenicity classifications and is provided for informational purposes only. CADD phred-like score integration into pathogencity classification is coming soon!

  • More variants have been manually-curated by the MORL
  • Variant Search Functionality

    There is now a variant search bar at the top of DVD webpages enabling the search of a specific variant, variants at a position, and/or variants in between a range of positions. The search bar is supported by an api interface as well. For more information about our api please see our API Documentation page. For more information about the search bar, please see our Help page.

  • Genome Browser

    A genome browser is now provided on gene pages for viewing gene level information in a track format.

    For more information regarding the genome browser plugin, please see BioDalliance's webpage.

  • Variant View Population Bolds and Highlights

    In the variant views (both the overlay and the full page), the max minor allele frequency(MAF) is bolded by source, and highlighted if it is the max MAF across all sources. Please keep in mind that the max MAF across all sources is a determining factor in variant classification.

    Exception: GnomaAD, although displayed, does not yet play a role in variant classification and is therefore not bolded nor highlighted.

  • Protein Structures via Force Field X (FFX)

    Protein structures are now provided on gene pages where available. These structures were modeled using Force Field X, an atomic resolution molecular modeling application.

    A promising source of evidence for classifying genetic variants is atomic resolution physics-based simulation techniques, which can test physical hypotheses about pathogenic mechanisms more rapidly and at a lower cost than many experimental approaches (e.g. model organisms). However, protein structural models (e.g. from X-ray crystallography, NMR, or homology modeling) required for simulation of hearing-related proteins are often based on imperfect experimental information (e.g. low-resolution diffraction) or may contain defects due to limited homology. We combine an advanced polarizable potential energy function, novel many-body optimization theory, and GPU-acceleration to locally and globally optimize all available deafness-associated protein models through the Force Field X (FFX) software program 1, 2, 3 . To objectively assess our models, we employed the MolProbity 4, 5 algorithm, which is widely used by crystallographers to aid refinement of models by reporting structural features that are known to be unphysical. Our optimization techniques improved the mean MolProbity score of 472 structures from 2.16 Å to 1.04 Å, consistent with protein structural models that approach atomic resolution.

    1. Tollefson, M. R. et al. (2018) OtoProtein: A Structural Database for Understanding Hearing Loss Genetics from GPU-Accelerated Polarizable Protein Side-Chain Repacking, In Progress.
    2. Fenn, T. D., and Schnieders, M. J. (2011) Polarizable atomic multipole X-ray refinement: Weighting schemes for macromolecular diffraction, Acta Crystallogr. D 67, 957-965.
    3. LuCore, S. D., Litman, J. M., Powers, K. T., Lynn, A. M., Gao, S., Tollefson, W. T. A., Fenn, T. D., Washington, M. T., and Schnieders, M. J. (2015) Dead-End Elimination for Many-Body Potentials Repacks Low-Resolution X-ray Diffraction Models into Atomic Resolution Structures, Proc. Natl. Acad. Sci. U.S.A.
    4. Chen, V.B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallographica Section D-Biological Crystallography 66, 12-21 (2010).
    5. Davis, I.W. et al. MolProbity: all-atom contacts and structure validation for proteins and nucleic acids. Nucleic Acids Research 35, W375-W383 (2007).

    For information on the structure viewer plugin, please see NGL Viewer's github.

Version 8.1 changes

  • Four genes have been renamed to match HUGO-approved gene symbols: ADGRV1 (GPR98), WHRN (DNB31), PJVK (DFNB59), TWNK (C10orf2)
  • More variants have been manually-curated by the MORL

Version 8.0 changes

  • Genes added: ATP6V1B1, CD164, CDC14A, EPS8L2, FGF3, FGFR1, FGFR2, GATA3, KITLG, LOXL3, MCM2, MET, PEX1, PEX6, ROR1, S1PR2, TBX1
  • More variants have been manually-curated by the MORL
  • A new downloadable version of the DVD is now available here

Version 7.0 changes

  • Genes removed: CATSPER2, CRYL1, GTPBP3, MIR182, MIR183, MTO1, TFB1M, TRMU
  • Minor allele frequencies from ExAC are now included
  • Minor allele frequencies from 1000 Genomes have been updated from Phase 1 to Phase 3
  • ClinVar annotations have been updated to the March 1, 2016 release
  • dbSNP rs IDs have been updated from Build 142 to Build 146
  • Prediction data have been updated from dbNSFP v2.1 to dbNSFP v3.0
  • A downloadable version of the DVD is now available here
  • More data from our in-house OtoDB have been curated and added
  • We have added more information on variant classifications and the nomenclature we use for the DVD