Comprehensive Cardiology Panel

Last modified: Jun 12, 2018

Summary

  • Is a 184 gene panel that includes assessment of non-coding variants
  • The Comprehensive Cardiology Panel covers known genetic causes of channelopathies and cardiomyopathies. It is ideal for patients in whom the phenotype is complex including features of both channelopathy and cardiomyopathy and for the investigation of sudden cardiac death as this panel includes all of our channelopathy and cardiomyopathy genes.

Analysis methods

  • PLUS
  • SEQ
  • DEL/DUP

Availability

4 weeks

Number of genes

184

Test code

CA1301

Panel size

Large

CPT codes

SEQ 81410
SEQ 81413
DEL/DUP 81414
SEQ 81439

Summary

The Blueprint Genetics Comprehensive Cardiology Panel (test code CA1301):

  • Is a 184 gene panel that includes assessment of selected non-coding disease-causing variants
  • Is available as PLUS analysis (sequencing analysis and deletion/duplication analysis), sequencing analysis only or deletion/duplication analysis only

ICD codes

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

ICD-10 Disease
Q24.8 Brugada syndrome
I42.5 RCM
I42.9 Cardiomyopathy NAS
Q87.1 Noonan syndrome
I49.9 Catecholaminergic polymorphic ventricular tachycardia (CPVT)
I46.2 Cardiac arrest underlying cardiac condition
I46.9 Cardiac arrest cause unspecified
I45.81 Long QT 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)
I49.9 Short QT syndrome

Sample Requirements

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 3μg
  • 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.

Subpanel description

This comprehensive panel includes genes from the following subpanels: Hypertrophic Cardiomyopathy (HCM) Panel, Dilated Cardiomyopathy (DCM) Panel, Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) Panel, Left Ventricular Non-Compaction Cardiomyopathy (LVNC) Panel, Long QT Syndrome (LQTS) Panel, Brugada Syndrome Panel, Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) Panel and Short QT Syndrome (SQTS) Panel

When a person dies suddenly and unexpectedly from a suspected cardiovascular cause, the term sudden cardiac death (SCD) is used. SCD is frequently caused by an abrupt change in heart rhythm (arrhythmia), most often ventricular tachycardia or ventricular fibrillation that impairs cardiac pumping, thereby depriving vital organs of oxygenated blood. A brief episode of VT or VF may cause only momentary loss of consciousness (syncope), but death is the inevitable result of sustained VF in the absence of emergent medical care. The differential diagnosis between ion channel disease and cardiomyopathies can be challenging on occasion as severe ventricular arrhythmias can manifest in cardiomyopathy patients with subclinical or no morphological cardiomyopathy.

Genes in the Comprehensive Cardiology Panel and their clinical significance

Gene Associated phenotypes Inheritance ClinVar HGMD
AARS2 Leukoencephalopathy, progressive, with ovarian failure, Combined oxidative phosphorylation deficiency 8 AR 17 26
ABCC6* Pseudoxanthoma elasticum AR 368 374
ABCC9 Atrial fibrillation, Cantu syndrome, Dilated cardiomyopathy (DCM) AD 25 40
ACAD9 Acyl-CoA dehydrogenase family, deficiency AR 25 44
ACADVL Acyl-CoA dehydrogenase, very long chain, deficiency AR 94 270
ACTA1 Myopathy AD/AR 61 206
ACTA2 Aortic aneurysm, familial thoracic, Moyamoya disease, Multisystemic smooth muscle dysfunction syndrome AD 20 72
ACTC1 Left ventricular noncompaction, Hypertrophic cardiomyopathy (HCM), Cardiomyopathy, restrictive, Atrial septal defect, Dilated cardiomyopathy (DCM) AD 23 60
ACTN2 Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 10 41
AGK* Sengers syndrome, Cataract 38 AR 18 27
AGL Glycogen storage disease AR 90 243
AKAP9 Long QT syndrome AD 4 33
ALMS1* Alström syndrome AR 64 295
ALPK3 Pediatric cardiomyopathy AR 9 5
ANK2 Cardiac arrhythmia, Long QT syndrome AD 7 70
ANO5 Gnathodiaphyseal dysplasia, LGMD2L and distal MMD3 muscular dystrophies AD/AR 60 115
APOA1 Amyloidosis, systemic nonneuronopathic, Hypoalphalipoproteinemia AD/AR 27 69
BAG3 Dilated cardiomyopathy (DCM), Myopathy, myofibrillar AD 36 60
BRAF* LEOPARD syndrome, Noonan syndrome, Cardiofaciocutaneous syndrome AD 135 65
CACNA1C* Brugada syndrome, Timothy syndrome AD 20 62
CACNB2 Brugada syndrome AD 3 22
CALM1* Ventricular tachycardia, catecholaminergic polymorphic, Recurrent cardiac arrest, infantile, Long QT syndrome AD 9 10
CALM2 Long QT syndrome AD 7 10
CALM3 Catecholaminergic polymorphic ventricular tachycardia AD/AR 4 4
CALR3 Cardiomyopathy, familial hypertrophic, 19 AD 3
CAPN3 Muscular dystrophy, limb-girdle, Eosinophilic myositis AR 134 428
CASQ2 Ventricular tachycardia, catecholaminergic, polymorphic AR 24 33
CAV3 Creatine phosphokinase, elevated serum, Hypertrophic cardiomyopathy (HCM), Long QT syndrome, Muscular dystrophy, limb-girdle, type IC, Myopathy, distal, Tateyama type, Rippling muscle disease 2 AD/Digenic 21 49
CBL Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia AD 23 38
CDH2 Arrhythmogenic right ventricular cardiomyopathy (ARVC) AD 5
COX15 Leigh syndrome, Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency AR 7 5
CPT2 Carnitine palmitoyltransferase II deficiency AR 48 107
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 15 28
CSRP3 Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 5 29
CTNNA3 Arrhythmogenic right ventricular dysplasia AD 6 41
DBH Dopamine beta-hydroxylase deficiency AR 10 13
DES Dilated cardiomyopathy (DCM), Myopathy, myofibrillar, Scapuloperoneal syndrome, neurogenic, Kaeser type AD/AR 61 117
DMD Becker muscular dystrophy, Duchenne muscular dystrophy, Dilated cardiomyopathy (DCM) XL 682 3818
DNAJC19 3-methylglutaconic aciduria AR 3 5
DOLK Congenital disorder of glycosylation AR 8 11
DSC2 Arrhythmogenic right ventricular dysplasia with palmoplantar keratoderma and woolly hair, Arrhythmogenic right ventricular dysplasia AD/AR 25 85
DSG2 Arrhythmogenic right ventricular dysplasia, Dilated cardiomyopathy (DCM) AD 40 125
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 155 281
DTNA Left ventricular noncompaction 1 AD 3 6
DYSF Miyoshi muscular dystrophy, Muscular dystrophy, limb-girdle, Myopathy, distal, with anterior tibial onset AR 188 517
EEF1A2 Epileptic encephalopathy, early infantile, Mental retardation AD 12 11
ELAC2 Combined oxidative phosphorylation deficiency 17 AR 11 15
EMD Emery-Dreifuss muscular dystrophy XL 44 112
ENPP1 Arterial calcification, Hypophosphatemic rickets AR 20 68
EPG5 Vici syndrome AR 29 50
ETFA Glutaric aciduria, Multiple acyl-CoA dehydrogenase deficiency AR 9 29
ETFB Glutaric aciduria, Multiple acyl-CoA dehydrogenase deficiency AR 6 14
ETFDH Glutaric aciduria, Multiple acyl-CoA dehydrogenase deficiency AR 41 173
FBXO32 Dilated cardiomyopathy (DCM) AD/AR 2
FHL1* Myopathy with postural muscle atrophy, Emery-Dreifuss muscular dystrophy, Reducing bod myopathy XL 22 60
FKRP Muscular dystrophy-dystroglycanopathy AR 41 137
FKTN Muscular dystrophy-dystroglycanopathy, Dilated cardiomyopathy (DCM), Muscular dystrophy-dystroglycanopathy (limb-girdle) AD/AR 34 57
FLNC* Myopathy AD 29 101
FOXD4* Dilated cardiomyopathy (DCM) AD 1
FOXRED1 Leigh syndrome, Mitochondrial complex I deficiency AR 15 8
FXN* Friedreich ataxia AR 12 63
GAA Glycogen storage disease AR 147 558
GATA5 Familial atrial fibrillation, Tetralogy of Fallot, Single ventricular septal defect AD/AR 5 31
GATA6 Heart defects, congenital, and other congenital anomalies, Atrial septal defect 9, atrioventricular septal defect 5, Persistent truncus arteriosus, Tetralogy of Fallot AD 16 79
GATAD1 Dilated cardiomyopathy (DCM) AR 23 1
GBE1 Glycogen storage disease AR 34 70
GFM1 Combined oxidative phosphorylation deficiency AR 18 18
GLA Fabry disease XL 215 919
GLB1 GM1-gangliosidosis, Mucopolysaccharidosis (Morquio syndrome) AR 65 212
GMPPB Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), Limb-girdle muscular dystrophy-dystroglycanopathy AR 14 35
GTPBP3 Combined oxidative phosphorylation deficiency 23 AR 14 15
GUSB* Mucopolysaccharidosis AR 26 61
HADHA Trifunctional protein deficiency, Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency AR 50 70
HAND1 Congenital heart defects, Dilated cardiomyopathy AD 8
HCN4 Sick sinus syndrome, Brugada syndrome AD 9 28
HFE Hemochromatosis AR/Digenic 10 56
HRAS Costello syndrome, Congenital myopathy with excess of muscle spindles AD 41 29
ISPD Muscular dystrophy-dystroglycanopathy AR 30 49
JPH2 Hypertrophic cardiomyopathy (HCM) AD 3 12
JUP Arrhythmogenic right ventricular dysplasia, Naxos disease AD/AR 8 43
KCNA5 Atrial fibrillation AD 4 23
KCNE1 Long QT syndrome, Jervell and Lange-Nielsen syndrome AD/AR/Digenic 7 45
KCNE2 Long QT syndrome, Atrial fibrillation, familial AD 6 23
KCNH2 Short QT syndrome, Long QT syndrome AD 346 925
KCNJ2 Short QT syndrome, Andersen syndrome, Long QT syndrome, Atrial fibrillation AD 41 87
KCNJ5 Long QT syndrome, Hyperaldosteronism, familial AD 7 15
KCNQ1 Short QT syndrome, Long QT syndrome, Atrial fibrillation, Jervell and Lange-Nielsen syndrome AD/AR/Digenic 285 604
KRAS* Noonan syndrome, Cardiofaciocutaneous syndrome AD 61 34
LAMA2 Muscular dystrophy, congenital merosin-deficient AR 125 294
LAMP2 Danon disease XL 57 97
LARGE Muscular dystrophy-dystroglycanopathy AR 16 25
LDB3 Dilated cardiomyopathy (DCM), Myopathy, myofibrillar AD 9 14
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 231 553
LRRC10 Dilated cardiomyopathy (DCM) AD/AR 4
LZTR1 Schwannomatosis, Noonan syndrome AD 27 64
MAP2K1 Cardiofaciocutaneous syndrome AD 45 21
MAP2K2 Cardiofaciocutaneous syndrome AD 21 35
MLYCD Malonyl-CoA decarboxylase deficiency AR 13 38
MTO1 Combined oxidative phosphorylation deficiency AR 15 24
MYBPC3 Left ventricular noncompaction, Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 460 1022
MYBPHL Dilated cardiomyopathy (DCM) AD 2
MYH6 Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM), Atrial septal defect 3 AD 13 114
MYH7 Hypertrophic cardiomyopathy (HCM), Myopathy, myosin storage, Myopathy, distal, Dilated cardiomyopathy (DCM) AD 285 950
MYL2 Hypertrophic cardiomyopathy (HCM), Infantile type I muscle fibre disease and cardiomyopathy AD 20 66
MYL3 Hypertrophic cardiomyopathy (HCM) AD/AR 13 40
MYL4 Atrial fibrillation, familial, 18 AD 2 2
MYOT Myopathy, myofibrillar, Muscular dystrophy, limb-girdle, 1A, Myopathy, spheroid body AD 7 16
MYPN Hypertrophic cardiomyopathy (HCM), Cardiomyopathy, restrictive, Dilated cardiomyopathy (DCM), Nemaline myopathy 11, autosomal recessive AD 5 43
NDUFAF2 Mitochondrial complex I deficiency, Leigh syndrome AR 10 8
NEXN Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 5 42
NF1* Watson syndrome, Neurofibromatosis, Neurofibromatosis-Noonan syndrome AD 810 2703
NKX2-5 Conotruncal heart malformations, Hypothyroidism, congenital nongoitrous,, Atrial septal defect, Ventricular septal defect 3, Conotruncal heart malformations, variable, Tetralogy of Fallot AD 43 102
NOS1AP Romano-Ward syndrome AD/AR 4
NRAS Noonan syndrome AD 31 14
NUP155 Atrial fibrillation 15 AR 2 1
PCCA Propionic acidemia AR 48 123
PCCB Propionic acidemia AR 41 114
PKP2* Arrhythmogenic right ventricular dysplasia AD 141 275
PLEC Muscular dystrophy, limb-girdle, Epidermolysis bullosa AR 33 98
PLEKHM2 Dilated cardiomyopathy (DCM), left ventricular noncompaction AR 1 1
PLN Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD/AR 8 29
PNPLA2 Neutral lipid storage disease with myopathy AR 12 36
POMT1 Muscular dystrophy-dystroglycanopathy AR 41 94
PPA2 Sudden cardiac failure, infantile AR 8 8
PPP1CB# Noonan syndrome-like disorder with loose anagen hair 2 AD 7 7
PRDM16 Left ventricular noncompaction, Dilated cardiomyopathy (DCM) AD 16 15
PRKAG2# Hypertrophic cardiomyopathy (HCM), Wolff-Parkinson-White syndrome, Glycogen storage disease of heart, lethal congenital AD 17 56
PTPN11 Noonan syndrome, Metachondromatosis AD 128 139
RAF1 LEOPARD syndrome, Noonan syndrome, Dilated cardiomyopathy (DCM) AD 44 48
RASA2# Noonan syndrome AD 1 3
RBCK1 Polyglucosan body myopathy AR 10 14
RBM20 Dilated cardiomyopathy (DCM) AD 19 43
RIT1 Noonan syndrome AD 20 25
RMND1* Combined oxidative phosphorylation deficiency AR 18 15
RRAS Noonan-syndrome like phenotype AD/AR 2
RYR2 Ventricular tachycardia, catecholaminergic polymorphic, Arrhythmogenic right ventricular dysplasia AD 113 353
SALL4 Acro-renal-ocular syndrome, Duane-radial ray/Okohiro syndrome AD 19 55
SCN1B Atrial fibrillation, Brugada syndrome, Generalized epilepsy with febrile seizures plus, Epilepsy, generalized, with febrile seizures plus, type 1, Epileptic encephalopathy, early infantile, 52 AD 15 29
SCN3B Atrial fibrillation, familial, Brugada syndrome AD 3 7
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 225 829
SCN10A Paroxysmal extreme pain disorder, Channelopathy-associated congenital insensitivity to pain, Primary erythermalgia, Sodium channelopathy-related small fiber neuropathy, Brugada syndrome AD/AR 1 70
SCNN1B Liddle syndrome, Pseudohypoaldosteronism, Bronchiectasis with or without elevated sweat chloride AD/AR 18 46
SCNN1G Liddle syndrome, Pseudohypoaldosteronism, Bronchiectasis with or without elevated sweat chloride AD/AR 5 18
SCO2 Leigh syndrome, Hypertrophic cardiomyopathy (HCM), Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency, Myopia AR 42 33
SDHA* Leigh syndrome/Mitochondrial respiratory chain complex II deficiency, Gastrointestinal stromal tumor, Paragangliomas, Dilated cardiomyopathy (DCM), Cardiomyopathy, dilated, 1GG AD/AR 42 58
SELENON Muscular dystrophy, rigid spine, Myopathy, congenital, with fiber- disproportion AR 32 62
SGCA Muscular dystrophy, limb-girdle AR 47 99
SGCB Muscular dystrophy, limb-girdle AR 29 62
SGCD Muscular dystrophy, limb-girdle, Dilated cardiomyopathy (DCM) AR 13 26
SGCG Muscular dystrophy, limb-girdle AR 20 63
SHOC2 Noonan-like syndrome with loose anagen hair AD 2 4
SLC22A5 Carnitine deficiency, systemic primary AR 84 150
SLC25A4 Progressive external ophthalmoplegia with mitochondrial DNA deletions, Mitochondrial DNA depletion syndrome AD/AR 12 15
SLC25A20 Carnitine-acylcarnitine translocase deficiency AR 14 42
SMCHD1 Facioscapulohumeral muscular dystrophy, Facioscapulohumeral muscular dystrophy, type 2 Digenic (involving a SMCHD1 mutation and permissive D4Z4 haplotype) 46 76
SOS1 Noonan syndrome AD 45 67
SOS2 Noonan syndrome 9 AD 3 6
SPEG Centronuclear myopathy 5 AR 5 8
SPRED1 Legius syndrome AD 23 71
TAB2 Congenital heart defects, multiple types, 2 AD 11 27
TAZ 3-Methylglutaconic aciduria, (Barth syndrome) XL 42 153
TBX5 Holt-Oram syndrome AD 55 126
TBX20* Atrial septal defect 4 AD 3 27
TCAP Muscular dystrophy, limb-girdle, Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD/AR 12 27
TECRL Ventricular tachycardia, catecholaminergic polymorphic, 3 AR 2 2
TGFB3 Loeys-Dietz syndrome (Reinhoff syndrome), Arrhythmogenic right ventricular dysplasia AD 17 22
TMEM43 Arrhythmogenic right ventricular dysplasia, Emery-Dreifuss muscular dystrophy AD 5 24
TMEM70 Mitochondrial complex V (ATP synthase) deficiency AR 11 18
TNNC1 Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 9 23
TNNI3 Hypertrophic cardiomyopathy (HCM), Cardiomyopathy, restrictive, Dilated cardiomyopathy (DCM) AD/AR 54 127
TNNI3K Cardiac conduction disease with or without dilated cardiomyopathy AD 1 2
TNNT2 Left ventricular noncompaction, Hypertrophic cardiomyopathy (HCM), Cardiomyopathy, restrictive, Dilated cardiomyopathy (DCM) AD 57 140
TOR1AIP1 Muscular dystrophy with progressive weakness, distal contractures and rigid spine AD/AR 2 5
TPM1 Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 33 95
TRDN Ventricular tachycardia, catecholaminergic polymorphic AR 10 6
TRIM32 Bardet-Biedl syndrome, Muscular dystrophy, limb-girdle AR 13 16
TRPM4 Progressive familial heart block AD 5 29
TSFM Combined oxidative phosphorylation deficiency AR 7 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 725 304
TTR Dystransthyretinemic hyperthyroxinemia, Amyloidosis, hereditary, transthyretin-related AD 49 146
VCL Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM) AD 8 29
VCP Amyotrophic lateral sclerosis, Inclusion body myopathy with early-onset Paget disease, Charcot-Marie-Tooth disease AD 18 57
VPS13A Choreoacanthocytosis AR 19 113
XK McLeod syndrome XL 10 39

* 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 the panel

Gene Genomic location HG19 HGVS RefSeq RS-number
ABCC6 Chr16:16281097 c.1780-29T>A NM_001171.5 rs72664206
ACADVL Chr17:7126948 c.1252-15A>G NM_001270447.1 rs765390290
ACADVL Chr17:7125485 c.822-11T>G NM_001270447.1
ACADVL Chr17:7125469 c.822-27C>T NM_001270447.1 rs374911841
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 Chr15:42695919 c.1746-20C>T NM_000070.2
CAPN3 Chr15:42702770 c.2185-16A>G NM_000070.2
CAPN3 Chr15:42678352 c.380-13T>A NM_000070.2
DMD ChrX:32644479 c.1332-11909C>G NM_004006.2
DMD ChrX:32841967 c.265-463A>G NM_004006.2
DMD ChrX:33192452 c.31+36947G>A NM_004006.2
DMD ChrX:32479520 c.3432+2036A>G NM_004006.2
DMD ChrX:32479316 c.3432+2240A>G NM_004006.2
DMD ChrX:32460274 c.3787-843C>A NM_004006.2
DMD ChrX:32398808 c.4675-11A>G NM_004006.2
DMD ChrX:32827744 c.531-16T>A/G NM_004006.2
DMD ChrX:32366860 c.5326-215T>G NM_004006.2
DMD ChrX:32360414 c.5740-15G>T NM_004006.2
DMD ChrX:32274692 c.6290+30954C>T NM_004006.2
DMD ChrX:31983146 c.6614+3310G>T NM_004006.2 rs797045526
DMD ChrX:31897527 c.6913-4037T>G NM_004006.2
DMD ChrX:31627738 c.8217+18052A>G NM_004006.2
DMD ChrX:31613687 c.8217+32103G>T NM_004006.2
DMD ChrX:32716130 c.832-15A>G NM_004006.2 rs72470513
DMD ChrX:31382270 c.9085-15519G>T NM_004006.2
DMD ChrX:31332523 c.9224+9192C>A 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:31279780 c.9225-647A>G NM_004006.2 rs398124091
DMD ChrX:31279781 c.9225-648A>G NM_004006.2 rs398124084
DMD ChrX:33032666 c.93+5590T>A NM_004006.2
DMD ChrX:31229031 c.9362-1215A>G NM_004006.2
DMD ChrX:31226400 c.9563+1215A>G 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:32669100 c.961-5831C>T NM_004006.2 rs398124099
DMD ChrX:32669194 c.961-5925A>C NM_004006.2
DMD ChrX:31219364 c.9807+2714C>T 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
ETFDH Chr4:159593534 c.-75A>G NM_004453.2
FKTN Chr9:108368857 c.648-1243G>T NM_006731.2
GAA Chr17:78078369 c.-17C>T NM_000152.3
GAA Chr17:78078341 c.-32-13T>A NM_000152.3
GAA Chr17:78078341 c.-32-13T>G NM_000152.3 rs386834236
GAA Chr17:78078352 c.-32-2A>G NM_000152.3
GAA Chr17:78078351 c.-32-3C>A NM_000152.3
GAA Chr17:78078351 c.-32-3C>A/G NM_000152.3
GAA Chr17:78082266 c.1076-22T>G NM_000152.3 rs762260678
GAA Chr17:78092432 c.2647-20T>G NM_000152.3
GATA5 Chr20:61051165 c.-201A>G NM_080473.4
GATA6 Chr18:19749272 c.-409C>G NM_005257.4
GATA6 Chr18:19749151 c.-530A>T NM_005257.4
GBE1 Chr3:81542963 c.2053-3358_2053-3350delGTGTGGTGGinsTGTTTTTTACATGACAGGT NM_000158.3
GLA ChrX:100656225 c.547+395G>C NM_000169.2
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
HFE Chr6:26087649 c.-20G>A NM_000410.3 rs138378000
KCNE2 Chr21:35736455 c.-13+5G>A NM_172201.1 rs786205806
KCNH2 Chr7:150646165 c.2399-28A>G NM_000238.3
LAMA2 Chr6:129636608 c.3556-13T>A NM_000426.3 rs775278003
LAMA2 Chr6:129714172 c.5235-18G>A NM_000426.3 rs188365084
LAMP2 ChrX:119604078 c.-1054A>C NM_001122606.1
LMNA Chr1:156107037 c.1608+14G>A NM_170707.3
LMNA Chr1:156107433 c.1609-12T>G NM_170707.3 rs267607582
LMNA Chr1:156100609 c.513+45T>G NM_170707.3
LMNA Chr1:156105681 c.937-11C>G NM_170707.3 rs267607645
LZTR1 Chr22:21340117 c.264-13G>A NM_006767.3 rs587777176
MLYCD Chr16:83948547 c.949-14A>G NM_012213.2 rs761146008
MYBPC3 Chr11:47353394 c.*26+2T>C NM_000256.3
MYBPC3 Chr11:47364832 c.1224-19G>A NM_000256.3 rs587776699
MYBPC3 Chr11:47364814 c.1224-1G>T NM_000256.3 rs767405420
MYBPC3 Chr11:47364815 c.1224-2A>G NM_000256.3 rs397515891
MYBPC3 Chr11:47364709 c.1227-13G>A NM_000256.3 rs397515893
MYBPC3 Chr11:47360310 c.2149-80G>A NM_000256.3
MYBPC3 Chr11:47359371 c.2309-26A>G NM_000256.3
MYBPC3 Chr11:47368581 c.906-1G>C NM_000256.3 rs587776700
MYBPC3 Chr11:47368616 c.906-36G>A NM_000256.3 rs864622197
NEXN Chr1:78381662 c.-52-78C>A NM_144573.3
NF1 Chr17:29422056 c.-272G>A NM_001042492.2
NF1 Chr17:29422055 c.-273A>C 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 Chr17:29488136 c.288+2025T>G NM_001042492.2
NF1 Chr17:29577934 c.4110+1802delA NM_001042492.2 rs863224944
NF1 Chr17:29577082 c.4110+945A>G NM_001042492.2
NF1 Chr17:29580296 c.4173+278A>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 Chr17:29508428 c.587-12T>A NM_001042492.2
NF1 Chr17:29508426 c.587-14T>A 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 Chr17:29685481 c.7971-17C>G NM_001042492.2
NF1 Chr17:29685177 c.7971-321C>G NM_001042492.2
NF1 Chr17:29685665 c.8113+25A>T 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
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 Chr6:118869417 c.-236C>G NM_002667.4 rs188578681
PLN Chr6:118869382 c.-271A>G NM_002667.4
POMT1 Chr9:134379574 c.-30-2A>G NM_007171.3
PTPN11 Chr12:112915602 c.934-59T>A NM_002834.3
SELENON Chr1:26143316 c.*1107T>C NM_020451.2
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
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
TRDN Chr6:123957870 c.22+29A>G NM_006073.3 rs774068079
VCP Chr9:35072710 c.-360G>C NM_007126.3

Test strength

The strengths of this test include:
  • CAP and ISO-15189 accreditations covering all operations at Blueprint Genetics including all Whole Exome Sequencing, NGS panels and confirmatory testing
  • 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 publically available analytic validation demonstrating complete details of test performance
  • ~1,500 non-coding disease causing variants in Blueprint WES assay (please see below ‘Non-coding disease causing variants covered by this panel’)
  • Our rigorous variant classification based on modified ACMG 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

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 comprehensive cardiology panel covers classical genes associated with Brugada syndrome, RCM, cardiomyopathy NAS, Noonan syndrome, catecholaminergic polymorphic ventricular tachycardia (CPVT), cardiac arrest underlying cardiac condition, cardiac arrest cause unspecified, syncope and collapse, abnormal ECG, Long QT syndrome, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), left ventricular non-compaction cardiomyopathy (LVNC) and Short QT syndrome. 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 Whole Exome Sequencing (WES) assay. All individual panels are sliced from WES data.

Sensitivity % (TP/(TP+FN) Specificity %
Single nucleotide variants 99.65% (412,456/413,893) >99.99%
Insertions, deletions and indels by sequence analysis
1-10 bps 96.94% (17,070/17,608) >99.99%
11-50 bps 99.07% (957/966) >99.99%
Copy number variants (exon level dels/dups)
Clinical samples (small CNVs, n=52)
1 exon level deletion 92.3% (24/26) NA
2 exons level deletion/duplication 100.0% (11/11) NA
3-7 exons level deletion/duplication 93.3% (14/15) NA
Microdeletion/-duplication sdrs (large CNVs, n=37))
Size range (0.1-47 Mb) 100% (37/37)
Simulated CNV detection
2 exons level deletion/duplication 90.98% (7,357/8,086) 99.96%
5 exons level deletion/duplication 98.63% (7,975/8,086) 99.98%
     
The performance presented above reached by WES with the following coverage metrics
     
Mean sequencing depth at exome level 174x
Nucleotides with >20x sequencing coverage (%) 99.4%

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 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 such as, 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, the customer has an access to details of the analysis, including patient specific sequencing metrics, a gene level coverage plot and a list of regions with inadequate coverage if present. This reflects our mission to build fully transparent diagnostics where customers have easy access to 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 of sequence variants is confirmation of variants classified as pathogenic or likely pathogenic using bi-directional Sanger sequencing. Variant(s) fulfilling all of the following criteria are not Sanger confirmed: 1) the variant quality score is above the internal threshold for a true positive call, 2) an unambiguous IGV in-line with the variant call and 3) previous Sanger confirmation of the same variant at least three times at Blueprint Genetics. Reported variants of uncertain significance are confirmed with bi-directional Sanger sequencing only if the quality score is below our internally defined quality score for true positive call. Reported copy number variations with a size <10 exons are confirmed by orthogonal methods such as qPCR if the specific CNV has been seen 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 used, congress abstracts and mutation databases to help our customers 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 within the family. In the case of variants of uncertain significance (VUS), we do not recommend family member risk stratification based on the VUS result. Furthermore, in the case of VUS, we do not recommend the use of genetic information in patient management or genetic counseling.

Our interpretation team analyzes millions of variants from thousands of individuals with rare diseases. Thus, our database, and our understanding of variants and related phenotypes, is growing by leaps and bounds. 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.

General resources