Core Cardiology Screen

The Core Cardiology Screen test is for healthy adults interested in learning about their genetic risk of developing certain cardiovascular diseases that can be monitored or even prevented before symptoms appear.

After receiving a positive result, healthcare provider can help their patient to make informed decisions about lifestyle choices or taking a preventive action.

These tests are for personal risk assessment of healthy individuals. Individuals with a family history of a hereditary disorder should have testing with the appropriate diagnostic panel instead of a Proactive Screen test.

All of the genes on the Core Cardiology Screen test are included on the Comprehensive Cardiology Screen test. However, the Core Cardiology Screen test contains only the most contributory genes where the clinical presentation is well-understood and the penetrance (likelihood that someone with a variant will develop symptoms) is high. For instance, the test does not include genes that cause classic Ehlers Danlos syndrome since cardiac involvement is rare in the classic form. HFE- associated hemochromatosis is not included as only approximately 10% of individuals who are homozygous for the most penetrant variant will develop the condition. This test does contain thrombosis susceptibility genes because the global health burden is significant even if the penetrance is not high.

The Core Cardiology Screen test includes screening for genes related to:
-Cardiomyopathy (HCM, DCM, ARVC)
-Channelopathies (LQTS, Brugada, CPVT)
-Dyslipidemia (FH)
-Vascular conditions (aortic disease, susceptibility to deep vein thrombosis/pulmonary embolism, Marfan syndrome, Loeys-Dietz syndrome, Ehlers Danlos syndrome (EDS) type 4)
-Pulmonary conditions (pulmonary arterial hypertension (PAH), alpha-1 antitrypsin deficiency, emphysema)
-Thrombophilia (F5 Leiden variant)
-Bleeding tendency (F5: only bi-allelic loss-of-function variants are reported)

Only variants classified as pathogenic or likely pathogenic based on an ACMG/AMP classification scheme will be reported.

The target region for each gene includes coding exons and ±20 base pairs from the exon-intron boundary. In addition, the panel includes non-coding and regulatory variants if listed above (Non-coding variants covered by the panel). Some regions of the gene(s) may be removed from the panel if specifically mentioned in the ‘Test limitations” section above. The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. Our pipeline is streamlined to maximize sensitivity without sacrificing specificity. We have incorporated a number of reference population databases and mutation databases including, but not limited, to 1000 Genomes Project, gnomAD, ClinVar and HGMD into our clinical interpretation software to make the process effective and efficient. For missense variants, in silico variant prediction tools such as SIFT, PolyPhen, MutationTaster are used to assist with variant classification. Through our online ordering and statement reporting system, Nucleus, ordering providers have access to the details of the analysis, including patient specific sequencing metrics, a gene level coverage plot and a list of regions with <20X sequencing depth if applicable. This reflects our mission to build fully transparent diagnostics where ordering providers can easily visualize the crucial details of the analysis process.

We provide customers with the most comprehensive report available on the market. Clinical interpretation requires a fundamental understanding of clinical genetics and genetic principles. At Blueprint Genetics, our PhD molecular geneticists prepare the report by assessing the pathogenicity of the identified variants. Our goal is to provide clinically meaningful reports that are understandable for all medical professionals regardless of whether they have formal training in genetics.  

Variant classification is the cornerstone of clinical interpretation and resulting patient management decisions. Our classifications follow the ACMG guideline 2015. Only variants classified as pathogenic or likely pathogenic based on an ACMG/AMP classification scheme will be reported.  

Our screening panel report includes tables for sequencing and copy number variants that include basic variant information (genomic coordinates, HGVS nomenclature, zygosity, allele frequencies, in silico predictions, OMIM phenotypes, and classification of the variant). In addition, the report includes descriptions of the variant and its association with disease. We also provide links to the references, abstracts, and variant databases used to help ordering providers further evaluate the reported findings if desired.  

Identification of pathogenic or likely pathogenic variants in dominant disorders or their combinations in different alleles in recessive disorders are considered molecular confirmation of the clinical diagnosis, or in proactive testing, to confer a risk of developing an inherited disease. In reproductive screening, identification of single pathogenic or likely pathogenic variants in genes related to recessive disorders is considered as a carriership. Disease risk of potential offspring depends on whether both parents have a pathogenic or likely pathogenic variant in the same gene. Reproductive risk related to X-linked disorders may be difficult to estimate due to the possibility of skewed X-chromosome inactivation. Genetic counseling is recommended whenever pathogenic or likely pathogenic variants are reported. 

Reporting focuses on high-quality variants that meet our stringent NGS quality metrics for a true positive call but they are not confirmed with alternative methods. Ordering healthcare professionals should consider further confirmation of the reported variants using a diagnostic test.