The website is created by research groups within the Victor Chang Cardiac Research Institute. For further information or queries regarding genes and/or variants, please contact chdgenes@victorchang.edu.au

Gene Curation Procedure

Existing CHD gene lists were extracted from the following sources: CHD gene panels of three different research studies (Blue et al.,1 La Haye et al.,2 Jia et al.,3), international diagnostic CHD gene panels (links below), CHD gene lists from two review papers and a manually curated list for a larger scale screen (Andersen et al.,4 Lalani et al.,5 Sifrim et al.,6). To potentially find additional genes with likely pathogenic/pathogenic variants on ClinVar that currently are not represented by a genes list, the following search was done: Starting with a broad search, in NCBI MedGen the search term "heart" was used. All heart-related diseases were checked for likely-pathogenic and pathogenic variants. If such variants were recorded in ClinVar, then the associated genes were added to a genes list called "MedGen/ClinVar heart compilation". From this large list all duplicates and all genes present in one of the other lists were removed to obtain a list with non-gene panel heart disease genes. Genes associated with cardiomyopathies were not considered for further analysis.

The obtained lists of genes were compared, combined and curated based on stringent criteria with respect to human CHD caused by variants in these genes. Genes were only included in the database if variants in the respective gene have been reported as the monogenic cause for CHD (isolated or in the context of a syndrome) in at least three independent familial or sporadic cases in one or more separate publications. In contrast, we excluded genes whose evidence for disease causation is solely based on animal models, or genes which are only predicted to cause CHD based on expression and known protein function, or non-cardiac phenotypes resembling those of known CHD genes

CHD gene panels:

1. Blue GM, Kirk EP, Giannoulatou E, Dunwoodie SL, Ho JW, Hilton DC, White SM, Sholler GF, Harvey RP and Winlaw DS. Targeted next-generation sequencing identifies pathogenic variants in familial congenital heart disease. Journal of the American College of Cardiology. 2014;64:2498-506.

2. LaHaye S, Corsmeier D, Basu M, Bowman JL, Fitzgerald-Butt S, Zender G, Bosse K, McBride KL, White P and Garg V. Utilization of Whole Exome Sequencing to Identify Causative Mutations in Familial Congenital Heart Disease. Circulation Cardiovascular genetics. 2016;9:320-9.

3. Jia Y, Louw JJ, Breckpot J, Callewaert B, Barrea C, Sznajer Y, Gewillig M, Souche E, Dehaspe L, Vermeesch JR, Lambrechts D, Devriendt K and Corveleyn A. The diagnostic value of next generation sequencing in familial nonsyndromic congenital heart defects. American journal of medical genetics Part A. 2015;167A:1822-9.

4. Andersen TA, Troelsen Kde L and Larsen LA. Of mice and men: molecular genetics of congenital heart disease. Cellular and molecular life sciences : CMLS. 2014;71:1327-52.

5. Lalani SR and Belmont JW. Genetic basis of congenital cardiovascular malformations. European journal of medical genetics. 2014;57:402-13.

6. Sifrim A, Hitz MP, Wilsdon A, Breckpot J, Turki SH, Thienpont B, McRae J, Fitzgerald TW, Singh T, Swaminathan GJ, Prigmore E, Rajan D, Abdul-Khaliq H, Banka S, Bauer UM, Bentham J, Berger F, Bhattacharya S, Bu'Lock F, Canham N, Colgiu IG, Cosgrove C, Cox H, Daehnert I, Daly A, Danesh J, Fryer A, Gewillig M, Hobson E, Hoff K, Homfray T, Study I, Kahlert AK, Ketley A, Kramer HH, Lachlan K, Lampe AK, Louw JJ, Manickara AK, Manase D, McCarthy KP, Metcalfe K, Moore C, Newbury-Ecob R, Omer SO, Ouwehand WH, Park SM, Parker MJ, Pickardt T, Pollard MO, Robert L, Roberts DJ, Sambrook J, Setchfield K, Stiller B, Thornborough C, Toka O, Watkins H, Williams D, Wright M, Mital S, Daubeney PE, Keavney B, Goodship J, Consortium UK, Abu-Sulaiman RM, Klaassen S, Wright CF, Firth HV, Barrett JC, Devriendt K, FitzPatrick DR, Brook JD, Deciphering Developmental Disorders S and Hurles ME. Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing. Nature genetics. 2016;48:1060-5.