Congenital Structural Heart Disease Panel

SEQmethod-seq-icon Our Sequence Analysis is based on a proprietary targeted sequencing method OS-Seq™ and offers panels targeted for genes associated with certain phenotypes. A standard way to analyze NGS data for finding the genetic cause for Mendelian disorders. Results in 21 days. DEL/DUPmethod-dup-icon Targeted Del/Dup (CNV) analysis is used to detect bigger disease causing deletions or duplications from the disease-associated genes. Results in 21 days. PLUSmethod-plus-icon Plus Analysis combines Sequence + Del/Dup (CNV) Analysis providing increased diagnostic yield in certain clinical conditions, where the underlying genetic defect may be detectable by either of the analysis methods. Results in 21 days.

Test code: CA1501

The Blueprint Genetics Congenital Structural Heart Disease Panel is a 28-gene test for genetic diagnostics of patients with a congenital heart defect that typically associated with a hereditary disorder. The Panel covers genetics of diseases such as such as Alagille syndrome, aortic stenosis, atrial septal defect, Ebstein anomaly, Holt-Oram syndrome, hypoplastic left heart syndrome, pulmonary artery stenosis, supravalvular aortic stenosis, tetralogy of Fallot and ventricular septal defect.

Most cases of congenital heart defects (CHD) are sporadic, which means they occur in people with no family history of the disorder. However, first-degree relatives of people with CHD have an increased risk of being born with a heart defect. Some CHD cases, especially when associated with disorders, are inherited in an autosomal dominant manner. In rare cases autosomal recessive and X-linked inheritance has also been demonstrated. Genetic diagnosis should be considered in all cases with suspicion of syndrome or in certain cases with strong family history of heart defects. Genetic diagnosis can confirm clinical suspicion of hereditary disorder and assist in genetic counseling, and risk stratification among family members. Identification of the genetic cause can also modulate decision-making on patient's management. Consider also Blueprint Genetics Primary Ciliary Dyskinesia (PCD) Panel as CHDs are common in this patient group. Early detection and treatment of respiratory disease associated with PCD can improve the outcome of associated CHD. If patient has any suspicion of rasopathies consider Blueprint Genetics Noonan Panel. Blueprint Genetics also offers a whole genome-wide deletion/duplication analysis to detect all chromosomal abnormalities associated with CHDs.

About Congenital Structural Heart Disease

There are many types of congenital heart defects (CHD). They range from simple asymptomatic defects to complex defects with severe, life-threatening symptoms. CHDs are the most common type of birth defect and affect at least 8 out of every 1,000 newborns. Annually more than 35,000 babies in the United States are born with CHDs. Many of these defects are simple conditions and need no treatment or are easily fixed. Some babies are born with complex CHD and require special medical care. The diagnosis and treatment of complex heart defects has greatly improved over the past few decades. As a result, almost all children who have complex heart defects survive to adulthood and can live active, productive lives. However, many patients who have complex CHDs continue to need special heart care throughout their lives. In the United States, more than 1 million adults are living with congenital heart defects.


Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more.

Genes in the Congenital Structural Heart Disease Panel and their clinical significance
GeneAssociated phenotypesInheritanceClinVarHGMD
ACTA2Aortic aneurysm, familial thoracic, Moyamoya disease, Multisystemic smooth muscle dysfunction syndromeAD2170
ACTC1Left ventricular noncompaction, Hypertrophic cardiomyopathy (HCM), Cardiomyopathy, restrictive, Atrial septal defect, Dilated cardiomyopathy (DCM)AD2338
BMPR2Pulmonary hypertension, primary, Pulmonary venoocclusive diseaseAD49409
CHD7Isolated gonadotropin-releasing hormone deficiency, CHARGE syndromeAD128746
CTC1Cerebroretinal microangiopathy with calcifications and cystsAR1329
ELNCutis laxa, Supravalvular aortic stenosisAD67104
FLNAFrontometaphyseal dysplasia, Osteodysplasty Melnick-Needles, Otopalatodigital syndrome type 1, Otopalatodigital syndrome type 2, Terminal osseous dysplasia with pigmentary defectsXL86209
FOXC1Axenfeld-Rieger syndrome, Iridogoniodysgenesis, Peters anomalyAD21123
FOXH1Congenital heart malformations, HoloprosencephalyAD32
G6PC3Neutropenia, severe congenital, Dursun syndromeAR1237
GATA4Tetralogy of Fallot, Atrioventricular septal defect, Testicular anomalies with or without congenital heart disease, Ventricular septal defect, Atrial septal defectAD24147
GATA5Familial atrial fibrillation, Tetralogy of Fallot, Single ventricular septal defectAD/AR27
GATA6Heart defects, congenital, and other congenital anomaliesAD1568
GJA1*Oculodentodigital dysplasia mild type, Oculodentodigital dysplasia severe type, Syndactyly type 3AD23103
GJA5Progressive familial heart block, Atrial standstill, digenic, Atrial fibrillationAD/Digenic735
HRASCostello syndrome, Congenital myopathy with excess of muscle spindlesAD3026
JAG1Alagille syndromeAD102557
NF1*Watson syndrome, Neurofibromatosis, Neurofibromatosis-Noonan syndromeAD2612607
NKX2-5Conotruncal heart malformations, Hypothyroidism, congenital nongoitrous,, Atrial septal defectAD41101
NODALHeterotaxy, visceralAD423
NOTCH1Aortic valve diseaseAD2872
NOTCH2*Alagille syndrome, Hajdu-Cheney syndromeAD2156
TBX1Conotruncal anomaly face syndromeAD759
TBX5Holt-Oram syndromeAD32119
TFAP2BPatent ductus arteriosus, nonsyndromic, Char syndromeAD1014
TLL1Atrial septal defectAD36
ZFPM246,XY sex reversalAD1136
ZIC3Heterotaxy, visceral, VACTERL association, Congenital heart defects, nonsyndromicXL1240
  • * Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (; HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, The list of associated (gene specific) phenotypes are generated from CDG ( or Orphanet ( databases.

Blueprint Genetics offers a comprehensive Congenital Structural Heart Disease Panel that covers classical genes associated with Alagille syndrome, aorta stenosis, atrial septal defect, ebstein anomaly, holt-Oram syndrome, hypoplastic left heart syndrome, pulmonary artery stenosis, supravalvular aortic stenosis, tetralogy of Fallot and ventricular septal defect. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. Average sensitivity and specificity in Blueprint NGS Panels is 99.3% and 99.9% for detecting SNPs. Sensitivity to for indels vary depending on the size of the alteration: 1-10bps (96.0%), 11-20 bps (88.4%) and 21-30 bps (66.7%). The longest detected indel was 46 bps by sequence analysis. Detection limit for Del/Dup (CNV) analysis varies through the genome depending on exon size, sequencing coverage and sequence content. The sensitivity is 71.5% for single exon deletions and duplications and 99% for three exons’ deletions and duplications. We have validated the assays for different starting materials including EDTA-blood, isolated DNA (no FFPE) and saliva that all provide high-quality results. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile.

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. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (, the NHLBI GO Exome Sequencing Project (ESP;, the Exome Aggregation Consortium (ExAC;, ClinVar database of genotype-phenotype associations ( and the Human Gene Mutation Database ( The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (, Polyphen (, and Mutation Taster (

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

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ICD & CPT codes

CPT codes


ICD codes

Commonly used ICD-10 codes when ordering the Congenital Structural Heart Disease Panel

Q21.3Tetralogy of Fallot
Q87.2Holt-Oram syndrome
Q25.3Supravalvular aortic stenosis
Q44.7Alagille syndrome

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.

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