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  • Test code: 02101
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit
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Invitae Arrhythmia and Cardiomyopathy Comprehensive Panel

Test description

This test provides a comprehensive analysis of the genes associated with inherited arrhythmia and cardiomyopathy conditions. Given the clinical overlap between different arrhythmia and cardiomyopathy conditions, comprehensive testing enables a more efficient evaluation of multiple conditions based on a single indication for testing.

Individuals with clinical symptoms of an inherited arrhythmia or cardiomyopathy may benefit from genetic testing to establish or confirm diagnosis, clarify risks, or inform management. Asymptomatic individuals within a family with a known pathogenic variant may also benefit by avoiding activities and medications that can trigger symptoms.

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Primary panel (100 genes)

ABCC9 ACADVL ACTC1 ACTN2 AGL ALMS1 ALPK3 BAG3 BRAF CACNA1C CACNA1D CALM1 CALM2 CALM3 CASQ2 CBL CDH2 CPT2 CRYAB CSRP3 DES DMD DNAJC19 DOLK DSC2 DSG2 DSP ELAC2 EMD EYA4 FHL1 FKRP FKTN FLNC GAA GATA4 GATA5 GJA5 GLA HCN4 HRAS JUP KCNE1 KCNH2 KCNJ2 KCNQ1 KRAS LAMP2 LMNA LZTR1 MAP2K1 MAP2K2 MRAS MTO1 MYBPC3 MYH7 MYL2 MYL3 MYL4 MYLK3 NF1 NKX2-5 NRAS PCCA PCCB PKP2 PLN PPA2 PPCS PPP1CB PRKAG2 PTPN11 RAF1 RASA1 RBM20 RIT1 RYR2 SCN5A SDHA SGCD SHOC2 SLC22A5 SOS1 SOS2 SPRED1 TAZ TBX20 TCAP TMEM43 TMEM70 TNNC1 TNNI3 TNNI3K TNNT2 TPM1 TRDN TRPM4 TTN TTR VCL

Add-on Preliminary-evidence Genes for Arrhythmia and Cardiomyopathy (57 genes)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future.

A2ML1 AKAP9 ANK2 ANKRD1 CACNA2D1 CACNB2 CALR3 CAV3 CHRM2 CTF1 CTNNA3 DTNA FHL2 GATA6 GATAD1 GPD1L HAND1 ILK JPH2 KCNA5 KCND3 KCNE2 KCNE3 KCNE5 KCNJ5 KCNJ8 KCNK3 KIF20A KLF10 LAMA4 LDB3 LRRC10 MAP3K8 MED12 MYH6 MYLK2 MYOM1 MYOZ2 MYPN NEBL NEXN NPPA PDLIM3 PLEKHM2 PRDM16 RANGRF RASA2 RRAS SCN10A SCN1B SCN2B SCN3B SCN4B SLMAP SNTA1 TMPO TXNRD2

Add-on Sudden Unexpected Death in Epilepsy (SUDEP) Genes (11 genes)

The symptoms associated with arrhythmia and seizures can appear very similar and are known to co-occur in some cases. Some clinicians may wish to include a selection of genes associated with epilepsy for individuals with a differential diagnosis of arrhythmia vs. seizures, or a primary indication of arrhythmia and a family history of seizures.

DEPDC5 KCNA1 KCNQ2 KCNQ3 KCNT1 PCDH19 PRRT2 SCN1A SCN8A SCN9A SLC2A1

  • Alström syndrome
  • Andersen-Tawil syndrome
  • Arrhythmogenic right ventricular cardiomyopathy (ARVC)
  • Atrial fibrillation
  • Barth syndrome
  • Brugada syndrome (BrS)
  • Cantu syndrome
  • Carnitine palmitoyltransferase II (CPTII or CPT2) deficiency
  • Carvajal syndrome
  • Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
  • Combined oxidative phosphorylation deficiency (COXPD)
  • Congenital disorder of glycosylation DOLK-CDG (CDG-Im)
  • Danon disease
  • Dilated cardiomyopathy (DCM)
  • Dystrophinopathy
  • Dystrophy-dystroglycanopathy types A4, B4, C4, A5, B5 and C5
  • Emery-Dreifuss muscular dystrophy (EDMD)
  • Fabry disease
  • Glycogen storage disease type II (GSDII), also known as Pompe disease
  • Glycogen storage disease, type III (GSD III)
  • Hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis)
  • Hypertrophic cardiomyopathy (HCM)
  • Inherited cardiomyopathies
  • Jervell and Lange-Nielsen syndrome (JLNS)
  • Left ventricular noncompaction (LVNC)
  • Limb-girdle muscular dystrophy type 2F
  • Long QT syndrome (LQTS)
  • Naxos disease
  • Noonan-spectrum disorders
  • Primary carnitine deficiency
  • Propionic acidemia
  • Restrictive cardiomyopathy (RCM)
  • SDHA-related mitochondrial complex II deficiency
  • Short QT syndrome (SQTS)
  • Timothy syndrome
  • Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency
  • Wolff-Parkinson-White syndrome (WPW)

To view the complete clinical description of this panel, click here.

The majority of inherited arrhythmia, cardiomyopathy and Noonan-spectrum conditions exhibit an autosomal dominant inheritance pattern. Alstrom syndrome, Naxos disease, Carvajal syndrome, CASQ2-related CPVT, congenital disorder of glycosylation DOLK-CDG (CDG-Im), dystrophy-dystroglycanopathy (types A4, B4, C4, A5, B5 and C5), glycogen storage disease type III, ELAC2-related and MTO1-related combined oxidative phosphorylation deficiency, limb-girdle muscular dystrophy type 2F, Jervell and Lange-Nielsen syndrome, Naxos syndrome, primary carnitine deficiency, Pompe disease, PPA2-related arrhythmia, propionic acidemia, SDHA-related mitochondrial complex II deficiency, and TRDN-related arrhythmia are autosomal recessive. Barth syndrome, Danon disease, Dystrophinopathy, Emery-Dreifuss muscular dystrophy and KCNE5-related arrhythmia are X-linked.

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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
A2ML1 NM_144670.4
ABCC9 NM_005691.3
ACADVL NM_000018.3
ACTC1 NM_005159.4
ACTN2* NM_001103.3
AGL NM_000642.2
AKAP9 NM_005751.4
ALMS1 NM_015120.4
ALPK3 NM_020778.4
ANK2 NM_001148.4
ANKRD1* NM_014391.2
BAG3 NM_004281.3
BRAF NM_004333.4
CACNA1C* NM_000719.6; NM_001129840.1
CACNA1D NM_000720.3
CACNA2D1 NM_000722.3
CACNB2 NM_201590.2
CALM1 NM_006888.4
CALM2 NM_001743.4
CALM3 NM_005184.2
CALR3 NM_145046.4
CASQ2 NM_001232.3
CAV3 NM_033337.2
CBL NM_005188.3
CDH2 NM_001792.4
CHRM2 NM_000739.2
CPT2 NM_000098.2
CRYAB NM_001885.2
CSRP3 NM_003476.4
CTF1* NM_001330.3
CTNNA3 NM_013266.3
DEPDC5 NM_001242896.1
DES NM_001927.3
DMD* NM_004006.2
DNAJC19 NM_145261.3
DOLK NM_014908.3
DSC2 NM_024422.4
DSG2 NM_001943.3
DSP NM_004415.2
DTNA NM_001390.4
ELAC2 NM_018127.6
EMD NM_000117.2
EYA4 NM_004100.4
FHL1 NM_001449.4
FHL2 NM_201555.1
FKRP NM_024301.4
FKTN* NM_001079802.1
FLNC* NM_001458.4
GAA* NM_000152.3
GATA4 NM_002052.3
GATA5 NM_080473.4
GATA6 NM_005257.5
GATAD1 NM_021167.4
GJA5 NM_005266.6
GLA* NM_000169.2
GPD1L NM_015141.3
HAND1 NM_004821.2
HCN4 NM_005477.2
HRAS NM_005343.2
ILK NM_004517.3
JPH2 NM_020433.4
JUP NM_002230.2
KCNA1 NM_000217.2
KCNA5 NM_002234.3
KCND3 NM_004980.4
KCNE1 NM_000219.5
KCNE2 NM_172201.1
KCNE3 NM_005472.4
KCNE5 NM_012282.2
KCNH2 NM_000238.3
KCNJ2 NM_000891.2
KCNJ5 NM_000890.3
KCNJ8 NM_004982.3
KCNK3 NM_002246.2
KCNQ1 NM_000218.2
KCNQ2 NM_172107.2
KCNQ3 NM_004519.3
KCNT1 NM_020822.2
KIF20A NM_005733.2
KLF10 NM_005655.3
KRAS NM_004985.4
LAMA4 NM_002290.4
LAMP2 NM_002294.2
LDB3 NM_001080116.1; NM_001171610.1,NM_007078.3
LMNA NM_170707.3
LRRC10 NM_201550.3
LZTR1 NM_006767.3
MAP2K1 NM_002755.3
MAP2K2 NM_030662.3
MAP3K8 NM_005204.3
MED12 NM_005120.2
MRAS NM_012219.4
MTO1 NM_012123.3
MYBPC3* NM_000256.3
MYH6 NM_002471.3
MYH7 NM_000257.3
MYL2 NM_000432.3
MYL3 NM_000258.2
MYL4 NM_001002841.1
MYLK2 NM_033118.3
MYLK3 NM_182493.2
MYOM1 NM_003803.3
MYOZ2 NM_016599.4
MYPN NM_032578.3
NEBL NM_006393.2
NEXN NM_144573.3
NF1* NM_000267.3
NKX2-5 NM_004387.3
NPPA NM_006172.3
NRAS NM_002524.4
PCCA NM_000282.3
PCCB NM_000532.4
PCDH19 NM_001184880.1
PDLIM3 NM_014476.5
PKP2 NM_004572.3
PLEKHM2 NM_015164.2
PLN NM_002667.3
PPA2 NM_176869.2
PPCS NM_024664.3
PPP1CB NM_206876.1
PRDM16* NM_022114.3
PRKAG2 NM_016203.3
PRRT2 NM_145239.2
PTPN11 NM_002834.3
RAF1 NM_002880.3
RANGRF NM_016492.4
RASA1 NM_002890.2
RASA2 NM_006506.3
RBM20 NM_001134363.2
RIT1 NM_006912.5
RRAS NM_006270.4
RYR2 NM_001035.2
SCN10A NM_006514.3
SCN1A NM_001165963.1
SCN1B NM_199037.3; NM_001037.4
SCN2B NM_004588.4
SCN3B NM_018400.3
SCN4B NM_174934.3
SCN5A NM_198056.2
SCN8A* NM_014191.3; NM_001330260.1
SCN9A NM_002977.3
SDHA* NM_004168.3
SGCD NM_000337.5
SHOC2 NM_007373.3
SLC22A5 NM_003060.3
SLC2A1 NM_006516.2
SLMAP NM_007159.2
SNTA1 NM_003098.2
SOS1 NM_005633.3
SOS2 NM_006939.2
SPRED1 NM_152594.2
TAZ NM_000116.4
TBX20 NM_001077653.2
TCAP NM_003673.3
TMEM43 NM_024334.2
TMEM70 NM_017866.5
TMPO NM_003276.2
TNNC1 NM_003280.2
TNNI3 NM_000363.4
TNNI3K NM_015978.2
TNNT2 NM_001001430.2
TPM1 NM_001018005.1
TRDN NM_006073.3
TRPM4 NM_017636.3
TTN* NM_001267550.2
TTR NM_000371.3
TXNRD2 NM_006440.4
VCL NM_014000.2

ACTN2: Deletion/duplication analysis is not offered for exon 9.
ANKRD1: Deletion/duplication analysis is not offered for exons 3-4. Sequencing analysis for exons 4 includes only cds +/- 10 bp.
CACNA1C: Deletion/duplication and sequencing analysis is not offered for exons 44-45.
CTF1: Deletion/duplication and sequencing analysis is not offered for exon 1.
DMD: Analysis guarantees del/dup detection at single-exon resolution.
FKTN: Analysis includes the intronic variant NM_001079802.1:c.647+2084G>T (also known as NM_001079802.1:c.648-1243G>T) and the ~3 kb retrotransposon insertion in the 3' UTR at position NM_001079802‚Äã.1:c.*4392_*4393.
FLNC: Deletion/duplication analysis is not offered for exon 47. Sensitivity and specificity for single nucleotide variants, insertions and deletions in exons 47-48 may be reduced due to the presence of segmental duplications overlapping the region.
GAA: Analysis includes the promoter variant NM_000152.3:c.-32-13T>G as well as the common exon 18 deletion.
GLA: Analysis includes the intronic variant NM_000169.2:c.IVS4+919G>A.
MYBPC3: Analysis includes the intronic variants NM_000256.3:c.1224-52G>A and c.3628-41_3628-17del25.
NF1: Sequencing analysis for exons 2, 7, 25, 41, 48 includes only cds +/- 10 bp.
PRDM16: Deletion/duplication analysis is not offered for exon 1.
SCN8A: Analysis includes exon 6 of NM_001330260.1.
SDHA: Deletion/duplication analysis is not offered for this gene and sequencing analysis is not offered for exon 14. Sequencing analysis for exons 6-8 includes only cds +/- 10 bp.
TTN: Exons 45-46, 147, 149, 164, 172-201 (NM_001267550.2) are excluded from analysis. TTN variants are included in the primary report based on functional effect and/or location. A complete list of variants of uncertain significance, likely benign and benign variants in TTN is available upon request. Variants are named relative to the NM_001267550.2 (meta) transcript. Variants in the coding sequence and intronic boundaries of the clinically relevant NM_133378.4 (N2A) and fetal isoforms are reported (PMID: 25589632, 29598826, 29691892, 31660661), with the exception of the PEVK tandem repeat region (172-198) (PMID: 28040389).