Evaluating the Clinical Validity of Hypertrophic Cardiomyopathy Genes

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 View Item