Invitae Congenital Heart Defects and Heterotaxy Panel

Ordering
  • Test code: 04201
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Test description

The Invitae Congenital Heart Defects and Heterotaxy Panel analyzes up to 85 genes that are associated with congenital heart defects (isolated and syndromic) and/or laterality defects, including heterotaxy and situs inversus. These genes were selected based on currently available evidence and make up Invitae’s most comprehensive test for congenital heart defects.

This panel also includes genes associated with primary ciliary dyskinesia (PCD). There is significant clinical overlap between heterotaxy, PCD, and congenital heart defects, and it may be difficult to differentiate between these types of heart defects early in life.

This test may establish a genetic diagnosis, which would eliminate the need for serial gene testing. A genetic diagnosis may guide medical management, enabling a clinician to determine the need for additional evaluations, screenings, and procedures.

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Primary panel (78 genes)

ACTC1 ACVR2B ALMS1 ANKS6 ARMC4 BBS10 BCOR BRAF C21orf59 CBL CCDC103 CCDC114 CCDC151 CCDC39 CCDC40 CCDC65 CCNO CEP290 CFAP53 CHD7 DNAAF1 DNAAF2 DNAAF3 DNAAF5 DNAH11 DNAH5 DNAH8 DNAI1 DNAI2 DNAL1 DRC1 DYX1C1 ELN FOXH1 GATA4 GDF1 GJA1 GPC3 HRAS INVS JAG1 KRAS LEFTY2 MAP2K1 MAP2K2 MCIDAS MED13L MEIS2 MKS1 NEK8 NF1 NKX2-5 NKX2-6 NME8 NODAL NOTCH1 NOTCH2 NPHP3 NR2F2 NRAS NSD1 OFD1 PTPN11 RAF1 RIT1 RPGR RSPH1 RSPH4A RSPH9 SHOC2 SOS1 SPAG1 TBX1 TBX5 TTC8 ZIC3 ZMYND10 ZNF423

CEP290: Analysis includes the intronic variant NM_025114.3:c.2991+1655A>G.
MKS1: Analysis includes the intronic variant NM_017777.3: c.1408-35_1408-7del.
NOTCH2: Analysis is not offered for exons 1-4.
RPGR: Only the transcript associated with X-linked primary ciliary dyskinesia (XL PCD) is analyzed; therefore, this test is not appropriate for X-linked retinitis pigmentosa (XLRP) testing.

Add-on Preliminary-evidence Genes for Congenital Heart Defects (7 genes)

In addition to the primary panel, clinicians can also choose to include seven genes that have limited evidence of association with congenital heart defects (CHD). At this time, the association of these seven genes with CHD remains uncertain. However, some clinicians may wish to include genes that may prove to be clinically significant in the future. Visit our Preliminary-evidence genes page to learn more. These genes can be added at no additional charge.

CFAP52 CRELD1 GATA6 HAND1 MYH6 SMAD6 ZFPM2

  • Alagille syndrome
  • Alstrom syndrome
  • cardio-facio-cutaneous syndrome (CFC)
  • CHARGE syndrome
  • Costello syndrome
  • Holt-Oram syndrome
  • Legius syndrome
  • Noonan syndrome with multiple lentigines (NSML) – formerly known as LEOPARD syndrome
  • Meckel syndrome
  • neurofibromatosis type 1 (NF1)
  • Noonan syndrome
  • oculo-facio-cardio-dental syndrome
  • primary ciliary dyskinesia (PCD)
  • Simpson-Golabi-Behmel syndrome
  • Sotos syndrome
  • Williams syndrome
  • congenital heart defects
    • aortic valve disorder
    • atrial septal defect
    • atrioventricular septal defect
    • congenital heart defects
    • conotruncal heart malformations
    • heterotaxy
    • hypoplastic left heart syndrome
    • supravalvar aortic stenosis
    • tetralogy of Fallot
    • transposition of the great arteries
    • ventricular septal defect

Congenital heart disease—more commonly referred to as congenital heart defects (CHD)—is the most common birth defect, affecting 35,000-40,000 newborns each year in the US. It is a leading cause of childhood morbidity and mortality worldwide. CHD can occur in isolation or within a constellation of symptoms comprising a genetic syndrome.

Heterotaxy is the abnormal or irregular arrangement of the thoracoabdominal organs, including the heart, lungs, spleen, and gastrointestinal tract. A large proportion (~70%) of patients with heterotaxy have complex CHD. There is also significant clinical overlap among primary ciliary dyskinesia (PCD), heterotaxy and CHD. PCD is a genetic defect affecting the cilia—hair-like structures on the surface of cells. Ciliary movement in the lungs, nasal passageways, and ear canals protect the airways from infections. Ciliary movement is also important in the developing embryo as the internal organs are being positioned. Many patients with PCD are born with their internal organs reversed or mirrored from their original positions—a condition known as situs inversus totalis. Given the clinical overlap, it can be difficult to differentiate among CHD, heterotaxy and PCD early in life, and testing genes associated with all three conditions may be indicated for individuals with congenital heart defects.

The clinical sensitivity for this test is unknown. Structural heart defects are clinically and genetically heterogeneous, and the percentage of patients with congenital heart disease and a pathogenic variant in one of the genes offered in this panel has not been determined.

Congenital heart disease can be inherited in several patterns, including autosomal dominant, autosomal recessive, X-linked dominant, and X-linked recessive.

The penetrance, symptoms and associated risks of congenital heart defects depend upon the specific variants in the identified gene.

Congenital heart disease affects approximately 8–10 per 1,000 live births and is the single largest cause of infant morbidity and mortality worldwide. Epidemiologic studies suggest that a genetic or environmental cause for CHD is identifiable in approximately 20%–30% of cases, with 3%–5% of CHD due to a detectable single-gene disorder. The combined prevalence of the disorders tested for in this panel has not been determined.

This test may be considered for individuals who have congenital heart defects with or without additional congenital anomalies or syndromic features.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ACTC1 NM_005159.4
ACVR2B NM_001106.3
ALMS1 NM_015120.4
ANKS6 NM_173551.4
ARMC4 NM_018076.2
BBS10 NM_024685.3
BCOR NM_017745.5
BRAF NM_004333.4
C21orf59 NM_021254.2
CBL NM_005188.3
CCDC103 NM_213607.2
CCDC114 NM_144577.3
CCDC151 NM_145045.4
CCDC39 NM_181426.1
CCDC40 NM_017950.3
CCDC65 NM_033124.4
CCNO NM_021147.4
CEP290* NM_025114.3
CFAP52 NM_145054.4
CFAP53 NM_145020.3
CHD7 NM_017780.3
CRELD1 NM_001031717.3
DNAAF1 NM_178452.4
DNAAF2 NM_018139.2
DNAAF3 NM_001256714.1
DNAAF5 NM_017802.3
DNAH11 NM_001277115.1
DNAH5 NM_001369.2
DNAH8 NM_001206927.1
DNAI1 NM_012144.3
DNAI2 NM_023036.4
DNAL1 NM_031427.3
DRC1 NM_145038.3
DYX1C1 NM_130810.3
ELN NM_001278939.1
FOXH1 NM_003923.2
GATA4 NM_002052.3
GATA6 NM_005257.5
GDF1 NM_001492.5
GJA1 NM_000165.4
GPC3 NM_004484.3
HAND1 NM_004821.2
HRAS NM_005343.2
INVS NM_014425.3
JAG1 NM_000214.2
KRAS NM_004985.4
LEFTY2 NM_003240.3
MAP2K1 NM_002755.3
MAP2K2 NM_030662.3
MCIDAS NM_001190787.1
MED13L NM_015335.4
MEIS2 NM_170674.4
MKS1* NM_017777.3
MYH6 NM_002471.3
NEK8 NM_178170.2
NF1 NM_000267.3
NKX2-5 NM_004387.3
NKX2-6 NM_001136271.2
NME8 NM_016616.4
NODAL NM_018055.4
NOTCH1 NM_017617.3
NOTCH2* NM_024408.3
NPHP3 NM_153240.4
NR2F2 NM_021005.3
NRAS NM_002524.4
NSD1 NM_022455.4
OFD1 NM_003611.2
PTPN11 NM_002834.3
RAF1 NM_002880.3
RIT1 NM_006912.5
RPGR* NM_000328.2
RSPH1 NM_080860.3
RSPH4A NM_001010892.2
RSPH9 NM_152732.4
SHOC2 NM_007373.3
SMAD6 NM_005585.4
SOS1 NM_005633.3
SPAG1 NM_172218.2
TBX1 NM_080647.1
TBX5 NM_000192.3
TTC8 NM_198309.3
ZFPM2 NM_012082.3
ZIC3 NM_003413.3
ZMYND10 NM_015896.2
ZNF423 NM_015069.3

CEP290: Analysis includes the intronic variant NM_025114.3:c.2991+1655A>G.
MKS1: Analysis includes the intronic variant NM_017777.3: c.1408-35_1408-7del.
NOTCH2: Analysis is not offered for exons 1-4.
RPGR: Only the transcript associated with X-linked primary ciliary dyskinesia (XL PCD) is analyzed; therefore, this test is not appropriate for X-linked retinitis pigmentosa (XLRP) testing.