ARVD/C Genetic Variants Database

Curators: Paul van der Zwaag, Jan Jongbloed and Peter van Tintelen
Dept. of Genetics, University Medical Center Groningen, Groningen, The Netherlands

This database is a work in progress. It contains information from clinical research and other types of data on variants in genes causing Arrhythmogenic Right Ventricular Dysplasia/ Cardiomyopathy (ARVD/C).
Find variants/mutations
 

News

August 30, 2010.

Multiple presentations from the 2010 ESC Congress in Stockholm were added to the database:
  • Gandjbakhch et al. addressed the specific case of the pathogenicity of mutations in PKP2 exon 6, which are specific for the long isoform PKP2b. They observed that the short isoform PKP2a is the unique proteic isoform expressed in heart, suggesting that variants located in PKP2 exon 6 are rare polymorphisms that the systematic molecular screening of PKP2 exon 6 is useless in ARVC and could be abandoned.
    See article details
  • Christensen et al. analyzed the prevalence of TMEM43 mutations in a Danish cohort. They identified mutations in two families; one novel (c.705+7G>A) and one reported (S358L).
    See article details
  • O'Mahony et al. presented their recently added data on desmosomal mutations in DCM patients.
    See article details
  • Ortiz et al. analyzed the prevalence of mutations in an ARVD/C cohort from North West Spain. These results were also presented at the 2010 ESHG Conference in Gothenburg. See article details.

August 19, 2010.

Elliott et al. described the results of genetic testing in 100 unrelated patients with idiopathic dilated cardiomyopathy (DCM). 5 DCM patients were found to carry pathogenic desmosomal protein gene mutations; an additional 13 patients had sequence variants of uncertain pathogenic significance and were excluded from further comparative analysis. None of the 5 carriers of desmosomal mutations fulfilled current diagnostic criteria for ARVD/C, but 1 had fibrofatty change in the left ventricle at autopsy. They conclude that the study suggests that both clinical presentations can be caused by mutations in desmosomal protein genes.
See article details

August 17, 2010.

A manuscript on two novel mutations in the intracellular cadherin segment of DSG2 by Gehmlich et al. was added to the database. The results include functional work such as localization studies, binding assays and immuno-histochemistry. 
See article details

June 8, 2010.

La Gerche et al. described the results of genetic testing in athletes with complex arrhythmias of right ventricular origin and structural RV abnormalities to evaluate whether there is sufficient genetic overlap with ARVD/C to consider them the same or different entities. They found lower than expected rates of mutations in desmosomal genes, supporting the hypothesis that an ARVC-like phenotype may be acquired through intense exercise without an identifiable genetic predisposition.
See article details

View older news in the news archive.

Reference: van der Zwaag PA, Jongbloed JD, van den Berg MP, van der Smagt JJ, Jongbloed R, Bikker H, Hofstra RM, van Tintelen JP. A genetic variants database for arrhythmogenic right ventricular dysplasia/cardiomyopathy. Hum Mutat. 2009; 30(9): 1278-83.

General remarks/ Disclaimer

  • This software and data are provided to enhance knowledge and encourage progress in the scientific community and are to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of University Medical Center Groningen.
  • Reference sequences for the 8 genes in this database: DSC2 , DSG2, DSP, JUP, PKP2, TGFB3, TMEM43, TP63
  • Mutation nomenclature follows the standard reported here: http://www.hgvs.org/mutnomen/
  • Numbering of nucleotides starts at the first position of the methionine start-codon.
  • Controls are displayed as the number of mutations found in a number of control chromosomes.
  • The classification of the variants is as listed in the corresponding article(s).
    • Synonymous mutations not listed in dbSNP and not tested in controls are classified as Unclassified Variants.
    • To help interpret the effect of missense mutations, we provide data obtained from three in silico prediction methods: the Grantham score, PolyPhen and SIFT.
    • The classification of a variant can change as a result of (a) new publication(s). These changes will be listed under 'news'

Work on this database is financially supported by the Department of Genetics of the University Medical Center Groningen, the Netherlands,
and by a grant from the Netherlands Heart Foundation (2007B132).

Last update: August 30, 2010