Invitae Cardiomyopathy Comprehensive Panel
Test description
This test provides a comprehensive analysis of the genes associated with inherited cardiomyopathy conditions. Given the clinical overlap between different cardiomyopathy conditions, comprehensive testing enables a more efficient evaluation of multiple conditions based on a single indication.
Individuals with clinical symptoms of an inherited cardiomyopathy may benefit from diagnostic 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.
Genes tested
Primary panel
ABCC9 ACADVL ACTC1 ACTN2 AGL ALMS1 ALPK3 BAG3 BRAF CACNA1C CBL CPT2 CRYAB CSRP3 DES DMD DNAJC19 DOLK DSC2 DSG2 DSP ELAC2 EMD EYA4 FHL1 FKRP FKTN FLNC GAA GLA HCN4 HRAS JUP KRAS LAMP2 LMNA LZTR1 MAP2K1 MAP2K2 MRAS MTO1 MYBPC3 MYH7 MYL2 MYL3 MYLK3 NF1 NRAS PCCA PCCB PKP2 PLN 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 TTN TTR VCL
Add-on Preliminary-evidence Genes for Cardiomyopathy
A2ML1 ANKRD1 CALR3 CAV3 CDH2 CHRM2 CTF1 CTNNA3 DTNA FHL2 GATA4 GATA6 GATAD1 HAND1 ILK JPH2 KIF20A KLF10 LAMA4 LDB3 LRRC10 MAP3K8 MED12 MYH6 MYLK2 MYOM1 MYOZ2 MYPN NEBL NEXN NKX2-5 NPPA PDLIM3 PLEKHM2 PRDM16 RASA2 RRAS TMPO TXNRD2
Analyzes genes that are associated with cardiomyopathy, a broad group of conditions characterized by an enlarged, stiff or weakened heart muscle.
Order test
Primary panel (82 genes)
Customized gene selection (0 included, 0 excluded)
ABCC9 ACADVL ACTC1 ACTN2 AGL ALMS1 ALPK3 BAG3 BRAF CACNA1C CBL CPT2 CRYAB CSRP3 DES DMD DNAJC19 DOLK DSC2 DSG2 DSP ELAC2 EMD EYA4 FHL1 FKRP FKTN FLNC GAA GLA HCN4 HRAS JUP KRAS LAMP2 LMNA LZTR1 MAP2K1 MAP2K2 MRAS MTO1 MYBPC3 MYH7 MYL2 MYL3 MYLK3 NF1 NRAS PCCA PCCB PKP2 PLN 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 TTN TTR VCL
Add-on Preliminary-evidence Genes for Cardiomyopathy (39 genes)
Customized gene selection (0 included, 0 excluded)
Analyzes genes that are associated with cardiomyopathy, a broad group of conditions characterized by an enlarged, stiff or weakened heart muscle.
A2ML1 ANKRD1 CALR3 CAV3 CDH2 CHRM2 CTF1 CTNNA3 DTNA FHL2 GATA4 GATA6 GATAD1 HAND1 ILK JPH2 KIF20A KLF10 LAMA4 LDB3 LRRC10 MAP3K8 MED12 MYH6 MYLK2 MYOM1 MYOZ2 MYPN NEBL NEXN NKX2-5 NPPA PDLIM3 PLEKHM2 PRDM16 RASA2 RRAS TMPO TXNRD2
Clinical information
Disorders tested
- Alström syndrome
- Arrhythmogenic cardiomyopathy
- Arrhythmogenic right ventricular cardiomyopathy (ARVC)
- Barth syndrome
- Carnitine palmitoyltransferase II (CPTII or CPT2) deficiency
- Carvajal syndrome
- 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
- 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)
- Left ventricular noncompaction (LVNC)
- Limb-girdle muscular dystrophy type 2F
- Naxos disease
- Noonan-spectrum disorders
- Primary carnitine deficiency
- Propionic acidemia
- Restrictive cardiomyopathy (RCM)
- SDHA-related mitochondrial complex II deficiency
- Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency
- Wolff-Parkinson-White syndrome (WPW)
Clinical description
To view the complete clinical description of this panel, click here.
Inheritance
Most forms of isolated cardiomyopathy and cardiomyopathy due to an underlying Noonan-spectrum condition are autosomal dominant. Barth syndrome, Danon disease, dystrophinopathy, Emery-Dreifuss muscular dystrophy, Fabry disease are X-linked disorders. Alstrom syndrome, Naxos disease, Carvajal syndrome, 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, primary carnitine deficiency, Pompe disease, propionic acidemia, and SDHA-related mitochondrial complex II deficiency are autosomal recessive conditions. Dystrophinopathy, Emery-Dreifuss muscular dystrophy, Danon disease, and Barth syndrome are X-linked conditions.
Assay
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 | ||
| ALMS1 | NM_015120.4 | ||
| ALPK3 | NM_020778.4 | ||
| ANKRD1* | NM_014391.2 | ||
| BAG3 | NM_004281.3 | ||
| BRAF | NM_004333.4 | ||
| CACNA1C* | NM_000719.6; NM_001129840.1 | ||
| CALR3 | NM_145046.4 | ||
| 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 | ||
| 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 | ||
| GATA6 | NM_005257.5 | ||
| GATAD1 | NM_021167.4 | ||
| GLA* | NM_000169.2 | ||
| HAND1 | NM_004821.2 | ||
| HCN4 | NM_005477.2 | ||
| HRAS | NM_005343.2 | ||
| ILK | NM_004517.3 | ||
| JPH2 | NM_020433.4 | ||
| JUP | NM_002230.2 | ||
| 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 | ||
| 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 | ||
| PDLIM3 | NM_014476.5 | ||
| PKP2 | NM_004572.3 | ||
| PLEKHM2 | NM_015164.2 | ||
| PLN | NM_002667.3 | ||
| PPCS | NM_024664.3 | ||
| PPP1CB | NM_206876.1 | ||
| PRDM16* | NM_022114.3 | ||
| PRKAG2 | NM_016203.3 | ||
| PTPN11 | NM_002834.3 | ||
| RAF1 | NM_002880.3 | ||
| RASA1 | NM_002890.2 | ||
| RASA2 | NM_006506.3 | ||
| RBM20 | NM_001134363.2 | ||
| RIT1 | NM_006912.5 | ||
| RRAS | NM_006270.4 | ||
| RYR2 | NM_001035.2 | ||
| SCN5A | NM_198056.2 | ||
| SDHA* | NM_004168.3 | ||
| SGCD | NM_000337.5 | ||
| SHOC2 | NM_007373.3 | ||
| SLC22A5 | NM_003060.3 | ||
| 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 | ||
| 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.
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).
