Evaluating the Clinical Validity of Hypertrophic Cardiomyopathy Genes.
Full text not available from this repository.Item Type: | Article |
---|---|
Status: | Published |
Official URL: | https://doi.org/10.1161/CIRCGEN.119.002460 |
Journal or Publication Title: | Circulation: Genomic and Precision Medicine |
Volume: | 12 |
Number: | 2 |
Date: | 2019 |
Divisions: | Cardio Genomics Molecular Cardiology |
Depositing User: | General Admin |
Identification Number: | 10.1161/CIRCGEN.119.002460 |
ISSN: | 2574-8300 |
Date Deposited: | 17 Dec 2020 02:48 |
Abstract: | Background: Genetic testing for families with hypertrophic cardiomyopathy (HCM) provides a significant opportunity to improve care. Recent trends to increase gene panel sizes often mean variants in genes with questionable association are reported to patients. Classification of HCM genes and variants is critical, as misclassification can lead to genetic misdiagnosis. We show the validity of previously reported HCM genes using an established method for evaluating gene-disease associations. Methods: A systematic approach was used to assess the validity of reported gene-disease associations, including associations with isolated HCM and syndromes including left ventricular hypertrophy. Genes were categorized as having definitive, strong, moderate, limited, or no evidence of disease causation. We also reviewed current variant classifications for HCM in ClinVar, a publicly available variant resource. Results: Fifty-seven genes were selected for curation based on their frequent inclusion in HCM testing and prior association reports. Of 33 HCM genes, only 8 (24%) were categorized as definitive ( MYBPC3, MYH7, TNNT2, TNNI3, TPM1, ACTC1, MYL2, and MYL3); 3 had moderate evidence ( CSRP3, TNNC1, and JPH2; 33%); and 22 (66%) had limited (n=16) or no evidence (n=6). There were 12 of 24 syndromic genes definitively associated with isolated left ventricular hypertrophy. Of 4191 HCM variants in ClinVar, 31% were in genes with limited or no evidence of disease association. Conclusions: The majority of genes previously reported as causative of HCM and commonly included in diagnostic tests have limited or no evidence of disease association. Systematically curated HCM genes are essential to guide appropriate reporting of variants and ensure the best possible outcomes for HCM families. Keywords: genetic testing; heart failure; syndrome; uncertainty. |
Creators: | Creators Email Ingles, Jodie UNSPECIFIED Goldstein, Jennifer UNSPECIFIED Thaxton, Courtney UNSPECIFIED Caleshu, Colleen UNSPECIFIED Corty, Edward W. UNSPECIFIED Crowley, Stephanie B. UNSPECIFIED Dougherty, Kristen UNSPECIFIED Harrison, Steven M. UNSPECIFIED McGlaughon, Jennifer UNSPECIFIED Milko, Laura V. UNSPECIFIED Morales, Ana UNSPECIFIED Seifert, Bryce A. UNSPECIFIED Strande, Natasha UNSPECIFIED Thomson, Kate UNSPECIFIED Peter van Tintelen, J. UNSPECIFIED Wallace, Kathleen UNSPECIFIED Walsh, Roddy UNSPECIFIED Wells, Quinn UNSPECIFIED Whiffin, Nicola UNSPECIFIED Witkowski, Leora UNSPECIFIED Semsarian, Christopher UNSPECIFIED Ware, James S. UNSPECIFIED Hershberger, Ray E. UNSPECIFIED Funke, Birgit UNSPECIFIED |
Last Modified: | 17 Dec 2020 02:48 |
URI: | https://eprints.centenary.org.au/id/eprint/289 |
Actions (login required)
![]() |
View Item |