Cardiomyopathy Panel

Updated
Summary
  • Is a 177 gene panel that includes assessment of non-coding variants
  • Is ideal for patients with a clinical suspicion of atypical or complex cardiomyopathy phenotypes.

Analysis methods
  • PLUS
Availability

4 weeks

Number of genes

177

Test code

CA1201

Panel size

Large

CPT codes
81439

Summary

The Blueprint Genetics Cardiomyopathy Panel (test code CA1201):

ICD codes

Commonly used ICD-10 code(s) when ordering the Cardiomyopathy Panel

ICD-10 Disease
I49.9 Unspecified arrhythmia
I42.5 RCM
I42.9 Cardiomyopathy NAS
I51.7 Cardiomegaly
Q87.1 Noonan syndrome
I42.2 Hypertrophic cardiomyopathy (HCM)
I42.0 Dilated cardiomyopathy (DCM)
I42.8 Arrhythmogenic right ventricular cardiomyopathy (ARVC)
I42.8 Left ventricular non-compaction cardiomyopathy (LVNC)

Sample Requirements

  • Blood (min. 1ml) in an EDTA tube
  • Extracted DNA, min. 2 μg in TE buffer or equivalent
  • Saliva (Oragene DNA OG-500 kit/OGD-500 or OG-575 & OGD-575)

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. Read more about our sample requirements here.

Subpanel description

This comprehensive panel includes genes from the following panels: Hypertrophic Cardiomyopathy (HCM) Panel, Dilated Cardiomyopathy (DCM) Panel, Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) Panel and Left Ventricular Non-Compaction Cardiomyopathy (LVNC) Panel.

Cardiomyopathies are a group of severe cardiac diseases with a strong genetic background. Cardiomyopathies are all associated with significantly increased risk of heart failure and sudden cardiac death. According to the European Society of Cardiology (ESC) classification (Charron et al. 2010), cardiomyopathies can be divided into five subgroups according to structural and functional changes of the myocardium: 1) hypertrophic cardiomyopathy (HCM), 2) dilated cardiomyopathy (DCM), 3) arrhythmogenic right ventricular cardiomyopathy (ARVC), 4) restrictive cardiomyopathy (RCM) and 5) non-classified cardiomyopathies such as isolated left ventricular non-compaction cardiomyopathy (LVNC). Thousands of causative cardiomyopathy mutations have been characterized from more than 100 genes to date. These genes encode proteins making up the structure of the sarcomere, cytoskeleton, desmosome, ion channels or nuclear lamina, and proteins participating in Ca2+ handling during the contraction phase of action potential or affecting cardiac energy metabolism. In addition, there are several disorders that may result in congenital or early childhood-onset cardiomyopathty.

Genes in the Cardiomyopathy Panel and their clinical significance

Gene Associated phenotypes Inheritance ClinVar HGMD
AARS2 Leukoencephalopathy, progressive, with ovarian failure, Combined oxidative phosphorylation deficiency 8 AR 19 31
ABCC6* Pseudoxanthoma elasticum AR 352 377
ABCC9 Atrial fibrillation, Cantu syndrome, Dilated cardiomyopathy (DCM) AD 27 46
ACAD9 Acyl-CoA dehydrogenase family, deficiency AR 26 61
ACADVL Acyl-CoA dehydrogenase, very long chain, deficiency AR 119 282
ACTA1 Myopathy AD/AR 68 212
ACTC1 Left ventricular noncompaction, Hypertrophic cardiomyopathy (HCM), Cardiomyopathy, restrictive, Atrial septal defect, Dilated cardiomyopathy (DCM) AD 23 63
ACTN2 Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 11 44
AGK* Sengers syndrome, Cataract 38 AR 18 27
AGL Glycogen storage disease AR 142 245
ALMS1* Alström syndrome AR 197 302
ALPK3 Pediatric cardiomyopathy AR 12 6
ANO5 Gnathodiaphyseal dysplasia, LGMD2L and distal MMD3 muscular dystrophies AD/AR 64 121
APOA1 Amyloidosis, systemic nonneuronopathic, Hypoalphalipoproteinemia AD/AR 28 71
BAG3 Dilated cardiomyopathy (DCM), Myopathy, myofibrillar AD 39 62
BRAF* LEOPARD syndrome, Noonan syndrome, Cardiofaciocutaneous syndrome AD 134 65
CALR3 Cardiomyopathy, familial hypertrophic, 19 AD 3
CAPN3 Muscular dystrophy, limb-girdle, Eosinophilic myositis AR 184 437
CASQ2 Ventricular tachycardia, catecholaminergic, polymorphic AR 24 34
CASZ1 Dilated cardiomyopathy (DCM), Ventricular septal defect AD 3 2
CBL Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia AD 24 43
CDH2 Arrhythmogenic right ventricular cardiomyopathy (ARVC) AD 1 6
CHRM2 Dilated cardiomyopathy (DCM) AD/AR 1
COX15 Leigh syndrome, Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency AR 7 5
CPT2 Carnitine palmitoyltransferase II deficiency AR 72 111
CRYAB Cataract, myofibrillar myopathy and cardiomyopathy, Congenital cataract and cardiomyopathy, Dilated cardiomyopathy (DCM), Myopathy, myofibrillar, Cataract 16, multiple types, Myopathy, myofibrillar, fatal infantile hypertonic, alpha-B crystallin-related AD 14 28
CSRP3 Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 4 30
CTNNA3 Arrhythmogenic right ventricular dysplasia AD 7 46
DBH Dopamine beta-hydroxylase deficiency AR 10 11
DES Dilated cardiomyopathy (DCM), Myopathy, myofibrillar, Scapuloperoneal syndrome, neurogenic, Kaeser type AD/AR 64 124
DMD Becker muscular dystrophy, Duchenne muscular dystrophy, Dilated cardiomyopathy (DCM) XL 832 3915
DNAJC19 3-methylglutaconic aciduria AR 3 6
DOLK Congenital disorder of glycosylation AR 8 11
DPM3 Congenital disorder of glycosylation, Dilated cardiomyopathy (DCM), Limb-girdle muscular dystrophy AR 3 2
DSC2 Arrhythmogenic right ventricular dysplasia with palmoplantar keratoderma and woolly hair, Arrhythmogenic right ventricular dysplasia AD/AR 32 87
DSG2 Arrhythmogenic right ventricular dysplasia, Dilated cardiomyopathy (DCM) AD 44 129
DSP Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis, Arrhythmogenic right ventricular dysplasia, familial, Cardiomyopathy, dilated, with wooly hair and keratoderma, Keratosis palmoplantaris striata II, Epidermolysis bullosa, lethal acantholytic AD/AR 177 296
DTNA Left ventricular noncompaction 1 AD 3 7
DYSF Miyoshi muscular dystrophy, Muscular dystrophy, limb-girdle, Myopathy, distal, with anterior tibial onset AR 244 529
EEF1A2 Epileptic encephalopathy, early infantile, Mental retardation AD 17 12
ELAC2 Combined oxidative phosphorylation deficiency 17 AR 11 15
EMD Emery-Dreifuss muscular dystrophy XL 48 113
EPG5 Vici syndrome AR 36 66
ETFA Glutaric aciduria, Multiple acyl-CoA dehydrogenase deficiency AR 8 29
ETFB Glutaric aciduria, Multiple acyl-CoA dehydrogenase deficiency AR 6 15
ETFDH Glutaric aciduria, Multiple acyl-CoA dehydrogenase deficiency AR 43 190
FBXL4 Mitochondrial DNA depletion syndrome AR 55 47
FBXO32 Dilated cardiomyopathy (DCM) AD/AR 2
FHL1* Myopathy with postural muscle atrophy, Emery-Dreifuss muscular dystrophy, Reducing bod myopathy XL 26 62
FHOD3 Cardiomyopathy, familial hypertrophic AD 1
FKRP Muscular dystrophy-dystroglycanopathy AR 66 140
FKTN Muscular dystrophy-dystroglycanopathy, Dilated cardiomyopathy (DCM), Muscular dystrophy-dystroglycanopathy (limb-girdle) AD/AR 45 58
FLNC* Myopathy AD 54 109
FOXD4* Dilated cardiomyopathy (DCM) AD 1
FOXRED1 Leigh syndrome, Mitochondrial complex I deficiency AR 15 8
FXN* Friedreich ataxia AR 13 63
GAA Glycogen storage disease AR 193 573
GATA4* Tetralogy of Fallot, Atrioventricular septal defect, Testicular anomalies with or without congenital heart disease, Ventricular septal defect, Atrial septal defect AD 37 140
GATA6 Heart defects, congenital, and other congenital anomalies, Atrial septal defect 9, atrioventricular septal defect 5, Persistent truncus arteriosus, Tetralogy of Fallot AD 16 82
GATAD1 Dilated cardiomyopathy (DCM) AR 31 1
GATC* Cardiomyopathy, fatal AR 1
GBE1 Glycogen storage disease AR 36 70
GFM1 Combined oxidative phosphorylation deficiency AR 19 19
GLA Fabry disease XL 226 937
GLB1 GM1-gangliosidosis, Mucopolysaccharidosis (Morquio syndrome) AR 90 220
GMPPB Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), Limb-girdle muscular dystrophy-dystroglycanopathy AR 19 41
GSK3B Hypertrophic cardiomyopathy, Dilated cardiomyopathy (DCM) 2
GTPBP3 Combined oxidative phosphorylation deficiency 23 AR 14 15
GUSB* Mucopolysaccharidosis AR 27 62
HADHA Trifunctional protein deficiency, Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency AR 65 71
HAND1 Congenital heart defects, Dilated cardiomyopathy AD 9
HCN4 Sick sinus syndrome, Brugada syndrome, Left ventricular non-compaction cardiomyopathy (LVNC) AD 8 34
HFE Hemochromatosis AR/Digenic 11 56
HRAS Costello syndrome, Congenital myopathy with excess of muscle spindles AD 43 31
IDUA Mucopolysaccharidosis AR 105 282
ILK Dilated cardiomyopathy (DCM) AD/AR 10
ISPD Muscular dystrophy-dystroglycanopathy AR 38 53
JPH2 Hypertrophic cardiomyopathy (HCM) AD 3 13
JUP Arrhythmogenic right ventricular dysplasia, Naxos disease AD/AR 8 46
KLHL24 Epidermolysis bullosa simplex, generalized, with scarring and hair loss, Dilated cardiomyopathy (DCM), Hypertrophic cardiomyopathy (HCM) AD/AR 5 5
KRAS* Noonan syndrome, Cardiofaciocutaneous syndrome AD 63 35
LAMA2 Muscular dystrophy, congenital merosin-deficient AR 199 301
LAMP2 Danon disease XL 62 101
LARGE Muscular dystrophy-dystroglycanopathy AR 19 27
LDB3 Dilated cardiomyopathy (DCM), Myopathy, myofibrillar AD 9 14
LEMD2 Cataract 46, juvenile onset, Arrhythmogenic right ventricular cardiomyopathy (ARVC), Dilated cardiomyopathy (DCM) AR 1 1
LMNA Heart-hand syndrome, Slovenian, Limb-girdle muscular dystrophy, Muscular dystrophy, congenital, LMNA-related, Lipodystrophy (Dunnigan), Emery-Dreiffus muscular dystrophy, Malouf syndrome, Dilated cardiomyopathy (DCM), Mandibuloacral dysplasia type A, Progeria Hutchinson-Gilford type AD/AR 250 564
LMOD2 Familial dilated cardiomyopathy AR
LRRC10 Dilated cardiomyopathy (DCM) AD/AR 4
LZTR1 Schwannomatosis, Noonan syndrome AD/AR 34 71
MAP2K1 Cardiofaciocutaneous syndrome AD 45 23
MAP2K2 Cardiofaciocutaneous syndrome AD 21 35
MAP3K8 Noonan syndrome AD 1
MIPEP* Combined oxidative phosphorylation deficiency 31 AR 5 8
MLYCD Malonyl-CoA decarboxylase deficiency AR 14 38
MTO1# Combined oxidative phosphorylation deficiency AR 16 24
MYBPC3 Left ventricular noncompaction, Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 482 1048
MYBPHL Dilated cardiomyopathy (DCM) AD 3
MYH6 Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM), Atrial septal defect 3 AD 14 123
MYH7 Hypertrophic cardiomyopathy (HCM), Myopathy, myosin storage, Myopathy, distal, Dilated cardiomyopathy (DCM) AD 305 986
MYL2 Hypertrophic cardiomyopathy (HCM), Infantile type I muscle fibre disease and cardiomyopathy AD 21 67
MYL3 Hypertrophic cardiomyopathy (HCM) AD/AR 12 41
MYL4 Atrial fibrillation, familial, 18 AD 2 2
MYOT Myopathy, myofibrillar, Muscular dystrophy, limb-girdle, 1A, Myopathy, spheroid body AD 6 16
MYPN Hypertrophic cardiomyopathy (HCM), Cardiomyopathy, restrictive, Dilated cardiomyopathy (DCM), Nemaline myopathy 11, autosomal recessive AD 6 44
MYRF Congenital heart malformations, Congenital abnormalities of the kidney and urinary tract AD 1 1
NDUFAF2 Mitochondrial complex I deficiency, Leigh syndrome AR 9 8
NEXN Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 6 43
NF1* Watson syndrome, Neurofibromatosis, Neurofibromatosis-Noonan syndrome AD 1157 2901
NKX2-5 Conotruncal heart malformations, Hypothyroidism, congenital nongoitrous,, Atrial septal defect, Ventricular septal defect 3, Conotruncal heart malformations, variable, Tetralogy of Fallot AD 45 108
NONO Mental retardation, X-linked, syndrome 34, Left ventricular non-compaction cardiomyopathy (LVNC) XL 10 4
NRAP Dilated cardiomyopathy (DCM) AR 1 6
NRAS Noonan syndrome AD 31 14
PCCA Propionic acidemia AR 66 125
PCCB# Propionic acidemia AR 68 115
PKP2#* Arrhythmogenic right ventricular dysplasia AD 150 289
PLEC Muscular dystrophy, limb-girdle, Epidermolysis bullosa AR 36 103
PLEKHM2 Dilated cardiomyopathy (DCM), left ventricular noncompaction AR 1 1
PLN Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD/AR 8 30
PNPLA2 Neutral lipid storage disease with myopathy AR 13 35
PPA2 Sudden cardiac failure, infantile AR 8 8
PPCS Dilated cardiomyopathy (DCM) AR 4
PPP1CB Noonan syndrome-like disorder with loose anagen hair 2 AD 8 11
PRDM16 Left ventricular noncompaction, Dilated cardiomyopathy (DCM) AD 17 20
PRKAG2 Hypertrophic cardiomyopathy (HCM), Wolff-Parkinson-White syndrome, Glycogen storage disease of heart, lethal congenital AD 19 57
PTPN11 Noonan syndrome, Metachondromatosis AD 135 140
QRSL1 Mitochondrial multisystemic disorder AR 4 2
RAF1 LEOPARD syndrome, Noonan syndrome, Dilated cardiomyopathy (DCM) AD 45 53
RASA2 Noonan syndrome AD 1 3
RBCK1 Polyglucosan body myopathy AR 11 14
RBM20 Dilated cardiomyopathy (DCM) AD 19 47
RIT1 Noonan syndrome AD 23 26
RMND1* Combined oxidative phosphorylation deficiency AR 17 15
RRAS Noonan-syndrome like phenotype AD/AR 2
RYR2 Ventricular tachycardia, catecholaminergic polymorphic, Arrhythmogenic right ventricular dysplasia AD 124 372
SCN5A Heart block, nonprogressive, Heart block, progressive, Long QT syndrome, Ventricular fibrillation, Atrial fibrillation, Sick sinus syndrome, Brugada syndrome, Dilated cardiomyopathy (DCM) AD/AR/Digenic 234 899
SCNN1B Liddle syndrome, Pseudohypoaldosteronism, Bronchiectasis with or without elevated sweat chloride AD/AR 19 47
SCNN1G Liddle syndrome, Pseudohypoaldosteronism, Bronchiectasis with or without elevated sweat chloride AD/AR 8 20
SCO1 Mitochondrial complex IV deficiency AR 6 5
SCO2 Leigh syndrome, Hypertrophic cardiomyopathy (HCM), Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency, Myopia AR 42 37
SDHA* Leigh syndrome/Mitochondrial respiratory chain complex II deficiency, Gastrointestinal stromal tumor, Paragangliomas, Dilated cardiomyopathy (DCM), Cardiomyopathy, dilated, 1GG AD/AR 54 87
SELENON# Muscular dystrophy, rigid spine, Myopathy, congenital, with fiber- disproportion AR 38 63
SGCA Muscular dystrophy, limb-girdle AR 60 100
SGCB Muscular dystrophy, limb-girdle AR 37 64
SGCD Muscular dystrophy, limb-girdle, Dilated cardiomyopathy (DCM) AR 21 27
SGCG Muscular dystrophy, limb-girdle AR 33 63
SHOC2 Noonan-like syndrome with loose anagen hair AD 2 4
SLC22A5 Carnitine deficiency, systemic primary AR 98 151
SLC25A20 Carnitine-acylcarnitine translocase deficiency AR 15 42
SLC25A4 Progressive external ophthalmoplegia with mitochondrial DNA deletions, Mitochondrial DNA depletion syndrome AD/AR 12 14
SMCHD1 Facioscapulohumeral muscular dystrophy, Facioscapulohumeral muscular dystrophy, type 2 AD 51 79
SOS1 Noonan syndrome AD 44 71
SOS2 Noonan syndrome 9 AD 4 6
SPEG Centronuclear myopathy 5 AR 5 11
SPRED1 Legius syndrome AD 38 71
TAB2 Congenital heart defects, multiple types, 2 AD 13 31
TAZ 3-Methylglutaconic aciduria, (Barth syndrome) XL 45 158
TBX20* Atrial septal defect 4 AD 4 28
TBX5 Holt-Oram syndrome AD 61 127
TCAP Muscular dystrophy, limb-girdle, Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD/AR 12 28
TGFB3 Loeys-Dietz syndrome (Reinhoff syndrome), Arrhythmogenic right ventricular dysplasia AD 19 26
TMEM43 Arrhythmogenic right ventricular dysplasia, Emery-Dreifuss muscular dystrophy AD 4 24
TMEM70 Mitochondrial complex V (ATP synthase) deficiency AR 12 18
TNNC1 Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 9 24
TNNI3 Hypertrophic cardiomyopathy (HCM), Cardiomyopathy, restrictive, Dilated cardiomyopathy (DCM) AD/AR 56 129
TNNI3K Cardiac conduction disease with or without dilated cardiomyopathy AD 1 3
TNNT2 Left ventricular noncompaction, Hypertrophic cardiomyopathy (HCM), Cardiomyopathy, restrictive, Dilated cardiomyopathy (DCM) AD 61 148
TOR1AIP1 Muscular dystrophy with progressive weakness, distal contractures and rigid spine AD/AR 3 5
TPM1 Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 34 98
TRIM32 Bardet-Biedl syndrome, Muscular dystrophy, limb-girdle AR 13 16
TSFM# Combined oxidative phosphorylation deficiency AR 6 6
TTN* Dilated cardiomyopathy (DCM), Tibial muscular dystrophy, Limb-girdle muscular dystrophy, Hereditary myopathy with early respiratory failure, Myopathy, early-onset, with fatal cardiomyopathy (Salih myopathy), Muscular dystrophy, limb-girdle, type 2J AD 818 327
TTR Dystransthyretinemic hyperthyroxinemia, Amyloidosis, hereditary, transthyretin-related AD 52 148
VCL Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 8 30
VCP Amyotrophic lateral sclerosis, Inclusion body myopathy with early-onset Paget disease, Charcot-Marie-Tooth disease AD 17 61
VPS13A Choreoacanthocytosis AR 19 115
XK McLeod syndrome XL 10 41

* Some, or all, of the gene is duplicated in the genome. Read more.

# The gene has suboptimal coverage (means <90% of the gene’s target nucleotides are covered at >20x with mapping quality score (MQ>20) reads).

The sensitivity to detect variants may be limited in genes marked with an asterisk (*) or number sign (#)

Gene refers to the HGNC approved gene symbol; Inheritance refers to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR), X-linked (XL), X-linked dominant (XLD) and X-linked recessive (XLR); ClinVar refers to the number of variants in the gene classified as pathogenic or likely pathogenic in this database (ClinVar); HGMD refers to the 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 CGD or Orphanet databases.

Non-coding variants covered by Cardiomyopathy Panel

Gene Genomic location HG19 HGVS RefSeq RS-number
ABCC6 Chr16:16244424 c.4403+11C>G NM_001171.5 rs72664215
ABCC6 Chr16:16256835 c.3506+15G>A NM_001171.5 rs72664302
ABCC6 Chr16:16281097 c.1780-29T>A NM_001171.5 rs72664206
ABCC6 Chr16:16284246 c.1432-22C>A NM_001171.5 rs72664297
ACADVL Chr17:7123160 c.-144_-132delCCCAGCATGCCCCinsT NM_000018.3
ACADVL Chr17:7125469 c.822-27C>T NM_001270447.1 rs374911841
ACADVL Chr17:7125485 c.822-11T>G NM_001270447.1
ACADVL Chr17:7126199 c.1146+15C>T NM_001270447.1 rs202237278
ACADVL Chr17:7126948 c.1252-15A>G NM_001270447.1 rs765390290
ACADVL Chr17:7127894 c.1747+23C>T NM_001270447.1
ACTC1 Chr15:35080829 c.*1784T>C NM_005159.4
AGL Chr1:100381954 c.4260-12A>G NM_000028.2 rs369973784
APOA1 Chr11:116708299 c.-21+22G>A NM_000039.1
APOA1 Chr11:116708365 c.-65A>C NM_000039.1
CAPN3 Chr15:42678352 c.380-13T>A NM_000070.2
CAPN3 Chr15:42695919 c.1746-20C>T NM_000070.2
CAPN3 Chr15:42697047 c.-188G>C NM_173089.1
CAPN3 Chr15:42702715 c.2184+21G>A NM_000070.2 rs763572829
CAPN3 Chr15:42702770 c.2185-16A>G NM_000070.2
DMD ChrX:31165653 c.10554-18C>G NM_004006.2
DMD ChrX:31200680 c.9974+175T>A NM_004006.2
DMD ChrX:31224814 c.9564-30A>T NM_004006.2
DMD ChrX:31225211 c.9564-427T>G NM_004006.2
DMD ChrX:31226400 c.9563+1215A>G NM_004006.2
DMD ChrX:31229031 c.9362-1215A>G NM_004006.2
DMD ChrX:31241047 c.9361+117A>G NM_004006.2
DMD ChrX:31279293 c.9225-160A>G NM_004006.2
DMD ChrX:31279418 c.9225-285A>G NM_004006.2
DMD ChrX:31279420 c.9225-287C>A NM_004006.2
DMD ChrX:31279780 c.9225-647A>G NM_004006.2 rs398124091
DMD ChrX:31279781 c.9225-648A>G NM_004006.2 rs398124084
DMD ChrX:31332523 c.9224+9192C>A NM_004006.2
DMD ChrX:31382270 c.9085-15519G>T NM_004006.2
DMD ChrX:31613687 c.8217+32103G>T NM_004006.2
DMD ChrX:31627738 c.8217+18052A>G NM_004006.2
DMD ChrX:31697714 c.7661-11T>C NM_004006.2
DMD ChrX:31897527 c.6913-4037T>G NM_004006.2
DMD ChrX:31983146 c.6614+3310G>T NM_004006.2 rs797045526
DMD ChrX:32274692 c.6290+30954C>T NM_004006.2
DMD ChrX:32305833 c.6118-15A>G NM_004006.2
DMD ChrX:32360414 c.5740-15G>T NM_004006.2
DMD ChrX:32366860 c.5326-215T>G NM_004006.2
DMD ChrX:32379144 c.5325+1743_5325+1760delTATTAAAAAATGGGTAGA NM_004006.2
DMD ChrX:32398808 c.4675-11A>G NM_004006.2
DMD ChrX:32460274 c.3787-843C>A NM_004006.2
DMD ChrX:32470726 c.3603+2053G>C NM_004006.2
DMD ChrX:32479316 c.3432+2240A>G NM_004006.2
DMD ChrX:32479520 c.3432+2036A>G NM_004006.2
DMD ChrX:32669100 c.961-5831C>T NM_004006.2 rs398124099
DMD ChrX:32669194 c.961-5925A>C NM_004006.2
DMD ChrX:32716130 c.832-15A>G NM_004006.2 rs72470513
DMD ChrX:32756908 c.650-39498A>G NM_004006.2
DMD ChrX:32827744 c.531-16T>A/G NM_004006.2
DMD ChrX:32827744 c.531-16T>A NM_004006.2
DMD ChrX:32827744 c.531-16T>G NM_004006.2
DMD ChrX:32841967 c.265-463A>G NM_004006.2
DMD ChrX:33032666 c.93+5590T>A NM_004006.2
DMD ChrX:33192452 c.31+36947G>A NM_004006.2
DMD ChrX:33229483 c.-54T>A NM_004006.2
DSC2 Chr18:28683379 c.-1445G>C NM_024422.4 rs75494355
DYSF Chr2:71817308 c.3443-33A>G NM_003494.3 rs786205083
DYSF Chr2:71840553 c.4410+13T>G NM_003494.3
DYSF Chr2:71889030 c.4886+1249G>T NM_003494.3
DYSF Chr2:71900503 c.5668-824C>T NM_003494.3
DYSF Chr2:71913729 c.*107T>A NM_003494.3 rs11903223
EMD ChrX:153608559 c.266-27_266-10delTCTGCTACCGCTGCCCCC NM_000117.2
ETFDH Chr4:159593534 c.-75A>G NM_004453.2
ETFDH Chr4:159602711 c.176-636C>G NM_004453.2
FKRP Chr19:47249328 c.-272G>A NM_024301.4
FKTN Chr9:108368857 c.648-1243G>T NM_006731.2
GAA Chr17:78078341 c.-32-13T>G NM_000152.3 rs386834236
GAA Chr17:78078341 c.-32-13T>A NM_000152.3
GAA Chr17:78078351 c.-32-3C>A/G NM_000152.3
GAA Chr17:78078352 c.-32-2A>G NM_000152.3
GAA Chr17:78078353 c.-32-1G>C NM_000152.3
GAA Chr17:78078369 c.-17C>T NM_000152.3
GAA Chr17:78082266 c.1076-22T>G NM_000152.3 rs762260678
GAA Chr17:78090422 c.2190-345A>G NM_000152.3
GAA Chr17:78092432 c.2647-20T>G NM_000152.3
GATA4 Chr8:11561282 c.-989C>T NM_002052.3
GATA4 Chr8:11561369 c.-902G>T NM_002052.3
GATA4 Chr8:11561399 NM_002052.3 rs1195641788
GATA4 Chr8:11612500 c.910-55T>C NM_002052.3
GATA4 Chr8:11612745 c.997+103G>T NM_002052.3 rs113049875
GATA4 Chr8:11614418 c.998-26G>A NM_002052.3
GATA6 Chr18:19749151 c.-530A>T NM_005257.4
GATA6 Chr18:19749272 c.-409C>G NM_005257.4
GBE1 Chr3:81542964 c.2053-3358_2053-3350delGTGTGGTGGinsTGTTTTTTACATGACAGGT NM_000158.3 rs869320698
GLA ChrX:100653945 c.640-11T>A NM_000169.2
GLA ChrX:100654735 c.640-801G>A NM_000169.2 rs199473684
GLA ChrX:100654793 c.640-859C>T NM_000169.2 rs869312374
GLA ChrX:100656225 c.547+395G>C NM_000169.2
GMPPB Chr3:49761246 c.-87C>T NM_013334.3 rs780961444
HFE Chr6:26087649 c.-20G>A NM_000410.3 rs138378000
LAMA2 Chr6:129633984 c.3175-22G>A NM_000426.3 rs777129293
LAMA2 Chr6:129636608 c.3556-13T>A NM_000426.3 rs775278003
LAMA2 Chr6:129714172 c.5235-18G>A NM_000426.3 rs188365084
LAMA2 Chr6:129835506 c.8989-12C>G NM_000426.3 rs144860334
LMNA Chr1:156100609 c.513+45T>G NM_170707.3
LMNA Chr1:156105681 c.937-11C>G NM_170707.3 rs267607645
LMNA Chr1:156107037 c.1608+14G>A NM_170707.3
LMNA Chr1:156107433 c.1609-12T>G NM_170707.3 rs267607582
LZTR1 Chr22:21336623 c.-38T>A NM_006767.3
LZTR1 Chr22:21350968 c.2220-17C>A NM_006767.3 rs1249726034
MLYCD Chr16:83948547 c.949-14A>G NM_012213.2 rs761146008
MYBPC3 Chr11:47353394 c.*26+2T>C NM_000256.3
MYBPC3 Chr11:47353821 c.3628-12C>G NM_000256.3 rs371428751
MYBPC3 Chr11:47359371 c.2309-26A>G NM_000256.3
MYBPC3 Chr11:47360310 c.2149-80G>A NM_000256.3
MYBPC3 Chr11:47364709 c.1227-13G>A NM_000256.3 rs397515893
MYBPC3 Chr11:47364832 c.1224-19G>A NM_000256.3 rs587776699
MYBPC3 Chr11:47364865 c.1224-52G>A NM_000256.3 rs786204336
MYBPC3 Chr11:47365750 c.1091-575A>C NM_000256.3
MYBPC3 Chr11:47367305 c.1090+453C>T NM_000256.3
MYBPC3 Chr11:47368602 c.906-22G>A NM_000256.3 rs756267771
MYBPC3 Chr11:47368616 c.906-36G>A NM_000256.3 rs864622197
NEXN Chr1:78381662 c.-52-78C>A NM_144573.3
NF1 Chr17:29422055 c.-273A>C NM_001042492.2
NF1 Chr17:29422056 c.-272G>A NM_001042492.2
NF1 Chr17:29431417 c.60+9031_60+9035delAAGTT NM_001042492.2
NF1 Chr17:29475515 c.61-7486G>T NM_001042492.2
NF1 Chr17:29488136 c.288+2025T>G NM_001042492.2
NF1 Chr17:29508426 c.587-14T>A NM_001042492.2
NF1 Chr17:29508428 c.587-12T>A NM_001042492.2
NF1 Chr17:29510334 c.888+651T>A NM_001042492.2
NF1 Chr17:29510427 c.888+744A>G NM_001042492.2
NF1 Chr17:29510472 c.888+789A>G NM_001042492.2
NF1 Chr17:29527428 c.889-12T>A NM_001042492.2
NF1 Chr17:29530107 c.1260+1604A>G NM_001042492.2
NF1 Chr17:29533239 c.1261-19G>A NM_001042492.2
NF1 Chr17:29534143 c.1392+754T>G NM_001042492.2
NF1 Chr17:29540877 c.1393-592A>G NM_001042492.2
NF1 Chr17:29542762 c.1527+1159C>T NM_001042492.2 rs878853868
NF1 Chr17:29548419 c.1642-449A>G NM_001042492.2
NF1 Chr17:29549489 c.*481A>G NM_001128147.2
NF1 Chr17:29553439 c.2002-14C>G NM_001042492.2
NF1 Chr17:29554225 c.2252-11T>G NM_001042492.2
NF1 Chr17:29556025 c.2410-18C>G NM_001042492.2
NF1 Chr17:29556027 c.2410-16A>G NM_001042492.2
NF1 Chr17:29556028 c.2410-15A>G NM_001042492.2
NF1 Chr17:29556031 c.2410-12T>G NM_001042492.2
NF1 Chr17:29556839 c.2851-14_2851-13insA NM_001042492.2
NF1 Chr17:29557267 c.2991-11T>G NM_001042492.2
NF1 Chr17:29558777 c.3198-314G>A NM_001042492.2
NF1 Chr17:29563299 c.3974+260T>G NM_001042492.2
NF1 Chr17:29577082 c.4110+945A>G NM_001042492.2
NF1 Chr17:29580296 c.4173+278A>G NM_001042492.2
NF1 Chr17:29588708 c.4578-20_4578-18delAAG NM_001042492.2
NF1 Chr17:29588715 c.4578-14T>G NM_001042492.2
NF1 Chr17:29654479 c.5269-38A>G NM_001042492.2
NF1 Chr17:29656858 c.5610-456G>T NM_001042492.2
NF1 Chr17:29657848 c.5812+332A>G NM_001042492.2 rs863224491
NF1 Chr17:29661577 c.5813-279A>G NM_001042492.2
NF1 Chr17:29664375 c.6428-11T>G NM_001042492.2
NF1 Chr17:29664618 c.6642+18A>G NM_001042492.2
NF1 Chr17:29676126 c.7190-12T>A NM_001042492.2
NF1 Chr17:29676127 c.7190-11_7190-10insGTTT NM_001042492.2
NF1 Chr17:29685177 c.7971-321C>G NM_001042492.2
NF1 Chr17:29685481 c.7971-17C>G NM_001042492.2
NF1 Chr17:29685665 c.8113+25A>T NM_001042492.2
NKX2-5 Chr5:172662741 NM_004387.3
NKX2-5 Chr5:172672291 c.-10205G>A .
NKX2-5 Chr5:172672303 c.-10217G>C .
PCCA Chr13:100958030 c.1285-1416A>G NM_000282.3
PCCB Chr3:136003251 c.714+462A>G NM_001178014.1
PLN Chr6:118869382 c.-271A>G NM_002667.4
PLN Chr6:118869417 c.-236C>G NM_002667.4 rs188578681
PTPN11 Chr12:112915602 c.934-59T>A NM_002834.3
RYR2 Chr1:237730106 c.3423+32dupG NM_001035.2
SCN5A Chr3:38639469 c.2024-11T>A NM_198056.2 rs777987317
SCN5A Chr3:38691021 c.-53+1G>A NM_198056.2
SELENON Chr1:26143316 c.*1107T>C NM_020451.2
SGCA Chr17:48246419 c.585-31_585-23delTCTGCTGAC NM_000023.2
SGCA Chr17:48246421 c.585-31_585-24delTCTGCTGA NM_000023.2
SGCA Chr17:48247492 c.748-12_748-11delCTinsAA NM_000023.2
SGCG Chr13:23755086 c.-127_-121delACAGTTG NM_000231.2 rs1422849467
SGCG Chr13:23755215 c.-1+1G>T NM_000231.2
SLC22A5 Chr5:131714054 c.394-16T>A NM_003060.3 rs775097754
SLC22A5 Chr5:131722665 c.825-52G>A NM_003060.3
SMCHD1 Chr18:2701019 c.1647+103A>G NM_015295.2
SMCHD1 Chr18:2705677 c.1843-15A>G NM_015295.2
SMCHD1 Chr18:2743740 c.3634-19A>G NM_015295.2
TAZ ChrX:153641699 n.694+4G>A NR_024048.1
TAZ ChrX:153649161 c.778-63_778-51delCTCCCAGGGCACC NM_000116.3 rs782249471
TBX20 Chr7:35293780 c.-549G>A NM_001077653.2 rs571512677
TBX5 Chr12:114704515 c.*88822C>A NM_000192.3 rs141875471
TGFB3 Chr14:76425035 c.*495C>T NM_003239.2 rs387906514
TGFB3 Chr14:76447266 c.-30G>A NM_003239.2 rs770828281
TPM1 Chr15:63349172 c.241-12_241-11delCTinsTG NM_001018005.1 rs199476309
VCP Chr9:35072710 c.-360G>C NM_007126.3

Added and removed genes from the panel

Genes added Genes removed
CASZ1
CHRM2
DPM3
FBXL4
FHOD3
GATA4
GATC
GSK3B
IDUA
ILK
KLHL24
LEMD2
LMOD2
MAP3K8
MIPEP
MYRF
NKX2-5
NONO
NRAP
PPCS
QRSL1
SCO1

Test Strengths

The strengths of this test include:
  • CAP and ISO-15189 accredited laboratory
  • CLIA-certified personnel performing clinical testing in a CLIA-certified laboratory
  • Powerful sequencing technologies, advanced target enrichment methods and precision bioinformatics pipelines ensure superior analytical performance
  • Careful construction of clinically effective and scientifically justified gene panels
  • Our Nucleus online portal providing transparent and easy access to quality and performance data at the patient level
  • Our publicly available analytic validation demonstrating complete details of test performance
  • ~2,000 non-coding disease causing variants in our clinical grade NGS assay for panels (please see below ‘Non-coding disease causing variants covered by this panel’)
  • Our rigorous variant classification scheme
  • Our systematic clinical interpretation workflow using proprietary software enabling accurate and traceable processing of NGS data
  • Our comprehensive clinical statements

Test Limitations

The following exons are not included in the panel as they are not sufficiently covered with high quality sequence reads: MTO1 (NM_133645:7;NM_001123226:8), PCCB (NM_001178014:4), PKP2 (NM_001254727:6), SELENON (NM_020451:3), TSFM (NM_001172696:5). Genes with suboptimal coverage in our assay are marked with number sign (#) and genes with partial, or whole gene, segmental duplications in the human genome are marked with an asterisk (*) if they overlap with the UCSC pseudogene regions. Gene is considered to have suboptimal coverage when >90% of the gene’s target nucleotides are not covered at >20x with mapping quality score (MQ>20) reads. The technology may have limited sensitivity to detect variants in genes marked with these symbols (please see the Panel content table above).

This test does not detect the following:
  • Complex inversions
  • Gene conversions
  • Balanced translocations
  • Mitochondrial DNA variants
  • Repeat expansion disorders unless specifically mentioned
  • Non-coding variants deeper than ±20 base pairs from exon-intron boundary unless otherwise indicated (please see above Panel Content / non-coding variants covered by the panel).
This test may not reliably detect the following:
  • Low level mosaicism (variant with a minor allele fraction of 14.6% is detected with 90% probability)
  • Stretches of mononucleotide repeats
  • Indels larger than 50bp
  • Single exon deletions or duplications
  • Variants within pseudogene regions/duplicated segments

The sensitivity of this test may be reduced if DNA is extracted by a laboratory other than Blueprint Genetics.

For additional information, please refer to the Test performance section and see our Analytic Validation.

The Blueprint Genetics cardiomyopathy panel covers classical genes associated with unspecified arrhythmia, RCM, cardiomyopathy NAS, cardiomegaly, Noonan syndrome, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), left ventricular non-compaction cardiomyopathy (LVNC) and endocardial fibroelastosis. The genes on the panel have been carefully selected based on scientific literature, mutation databases and our experience.

Our panels are sliced from our high-quality whole exome sequencing data. Please see our sequencing and detection performance table for different types of alterations at the whole exome level (Table).

Assays have been validated for different starting materials including EDTA-blood, isolated DNA (no FFPE), saliva and dry blood spots (filter card) and all provide high-quality results. The diagnostic yield varies substantially depending on the assay used, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find a molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be a cost-effective first line test if your patient’s phenotype is suggestive of a specific mutation type.

Performance of Blueprint Genetics high-quality, clinical grade NGS sequencing assay for panels.

Sensitivity % (TP/(TP+FN) Specificity %
Single nucleotide variants 99.89% (99,153/99,266) >99.9999
Insertions, deletions and indels by sequence analysis
1-10 bps 96.9% (7,563/7,806) >99.9999
11-50 bps 99.13% (2,524/2,546) >99.9999
Copy number variants (exon level dels/dups)
1 exon level deletion (heterozygous) 100% (20/20) NA
1 exon level deletion (homozygous) 100% (5/5) NA
1 exon level deletion (het or homo) 100% (25/25) NA
2-7 exon level deletion (het or homo) 100% (44/44) NA
1-9 exon level duplication (het or homo) 75% (6/8) NA
Simulated CNV detection
5 exons level deletion/duplication 98.7% 100.00%
Microdeletion/-duplication sdrs (large CNVs, n=37))
Size range (0.1-47 Mb) 100% (37/37)
     
The performance presented above reached by WES with the following coverage metrics
     
Mean sequencing depth at exome level 143X
Nucleotides with >20x sequencing coverage (%) 99.86%

Bioinformatics

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.

Clinical interpretation

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

Variant classification is the corner stone of clinical interpretation and resulting patient management decisions. Our classifications follow the Blueprint Genetics Variant Classification Schemes based on the ACMG guideline 2015. Minor modifications were made to increase reproducibility of the variant classification and improve the clinical validity of the report. Our experience with tens of thousands of clinical cases analyzed at our laboratory allowed us to further develop the industry standard.

The final step in the analysis is orthogonal confirmation. Sequence variants classified as pathogenic, likely pathogenic and variants of uncertain significance (VUS) are confirmed using bi-directional Sanger sequencing when they do not meet our stringent NGS quality metrics for a true positive call.
Reported heterozygous and homo/hemizygous copy number variations with a size <10 and <3 target exons are confirmed by orthogonal methods such as qPCR if the specific CNV has been seen and confirmed less than three times at Blueprint Genetics.

Our clinical statement 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 statement includes detailed descriptions of the variant, gene and phenotype(s) including the role of the specific gene in human disease, the mutation profile, information about the gene’s variation in population cohorts and detailed information about related phenotypes. We also provide links to the references, abstracts and variant databases used to help ordering providers further evaluate the reported findings if desired. The conclusion summarizes all of the existing information and provides our rationale for the classification of the variant.

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. In these cases, family member testing can be used for risk stratification. We do not recommend using variants of uncertain significance (VUS) for family member risk stratification or patient management. Genetic counseling is recommended.

Our interpretation team analyzes millions of variants from thousands of individuals with rare diseases. Our internal database and our understanding of variants and related phenotypes increases with every case analyzed. Our laboratory is therefore well-positioned to re-classify previously reported variants as new information becomes available. If a variant previously reported by Blueprint Genetics is re-classified, our laboratory will issue a follow-up statement to the original ordering health care provider at no additional cost.

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