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Clinical impact of re-evaluating genes and variants implicated in dilated cardiomyopathy
Clinical impact of re-evaluating genes and variants implicated in dilated cardiomyopathy
- Source :
- Genetics in Medicine; 2186; 2193; 1098-3600; 11; 23; ~Genetics in Medicine~2186~2193~~~1098-3600~11~23~~
- Publication Year :
- 2021
-
Abstract
- Contains fulltext : 243935.pdf (Publisher’s version ) (Open Access)<br />PURPOSE: Accurate interpretation of variants detected in dilated cardiomyopathy (DCM) is crucial for patient care but has proven challenging. We applied a set of proposed refined American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria for DCM, reclassified all detected variants in robust genes, and associated these results to patients' phenotype. METHODS: The study included 902 DCM probands from the Maastricht Cardiomyopathy Registry who underwent genetic testing. Two gene panel sizes (extended n = 48; and robust panel n = 14) and two standards of variant classification (standard versus the proposed refined ACMG/AMP criteria) were applied to compare genetic yield. RESULTS: A pathogenic or likely pathogenic (P/LP) variant was found in 17.8% of patients, and a variant of uncertain significance (VUS) was found in 32.8% of patients when using method 1 (extended panel (n = 48) + standard ACMG/AMP), compared to respectively 16.9% and 12.9% when using method 2 (robust panel (n = 14) + standard ACMG/AMP), and respectively 14% and 14.5% using method 3 (robust panel (n = 14) + refined ACMG/AMP). Patients with P/LP variants had significantly lower event-free survival compared to genotype-negative DCM patients. CONCLUSION: Stringent gene selection for DCM genetic testing reduced the number of VUS while retaining ability to detect similar P/LP variants. The number of genes on diagnostic panels should be limited to genes that have the highest signal to noise ratio.
Details
- Database :
- OAIster
- Journal :
- Genetics in Medicine; 2186; 2193; 1098-3600; 11; 23; ~Genetics in Medicine~2186~2193~~~1098-3600~11~23~~
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1377068509
- Document Type :
- Electronic Resource