Metabolic Myopathy and Rhabdomyolysis Panel

Summary
Is a 127 gene panel that includes assessment of non-coding variants.

In addition, it also includes the maternally inherited mitochondrial genome.
Is ideal for patients with a medical condition associated with rhabdomyolysis. The genes on this panel are included in the Comprehensive Metabolism Panel.

Analysis methods
  • PLUS
Availability
4 weeks
Number of genes
127
Test code
ME1401
Panel tier
Tier 2
CPT Code *
81161, 81404 x7, 81405 x15, 81406 x12, 81407 x2, 81408 x3, 81479, 81460, 81465
* The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Summary

The Blueprint Genetics Metabolic Myopathy and Rhabdomyolysis Panel (test code ME1401):

Read about our accreditations, certifications and CE-marked IVD medical devices here.

ICD Codes

Refer to the most current version of ICD-10-CM manual for a complete list of ICD-10 codes.

Sample Requirements

  • Blood (min. 1ml) in an EDTA tube
  • Extracted DNA, min. 2 μg in TE buffer or equivalent
  • Saliva (Please see Sample Requirements for accepted saliva kits)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

We do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue. In addition, if the patient is affected with a hematological malignancy, DNA extracted from a non-hematological source (e.g. skin fibroblasts) is strongly recommended.

Please note that, in rare cases, mitochondrial genome (mtDNA) variants may not be detectable in blood or saliva in which case DNA extracted from post-mitotic tissue such as skeletal muscle may be a better option.

Read more about our sample requirements here.

Rhabdomyolysis is a medical condition in which damaged striated skeletal muscles break down easily and rapidly. Some end products of this lysis, such as myoglobin, are toxic to kidneys and may cause acute renal failure. Symptoms include muscle pain and vomiting. Common and important causes of rhabdomyolysis include several common situations, such as drugs and toxins, infections, hyperthermia, strong physical exercise and car accidents. However, recurrent rhabdomyolysis is often genetic in nature. The genetic causes for rhabdomyolysis include metabolic myopathy, disorders of intramuscular calcium release, mitochondrial disorders and muscular dystrophies. Metabolic myopathies are a group of genetic muscular diseases resulting from defective metabolism affecting primarily muscles. These myopathies are typically subdivided into three categories: i) glycogen storage diseases, ii) lipid storage diseases and iii) disorders of purine metabolism, all of which are associated with specific enzymatic defects that prevent adequate energy and ATP levels for muscle cells. This panel includes genes associated with all medical conditions that can cause rhabdomyolysis of genetic origin. The prevalence of rhabdomyolysis is not known.

Genes in the Metabolic Myopathy and Rhabdomyolysis Panel and their clinical significance

To view complete table content, scroll horizontally.

GeneAssociated phenotypesInheritanceClinVarHGMD
ACAD9Acyl-CoA dehydrogenase family, deficiencyAR2661
ACADLLong chain acyl-CoA dehydrogenase deficiencyAD/AR1
ACADMAcyl-CoA dehydrogenase, medium chain, deficiencyAR104169
ACADVLAcyl-CoA dehydrogenase, very long chain, deficiencyAR119282
ADCK3Coenzyme Q10 deficiency, Progressive cerebellar ataxia and atrophy, Spinocerebellar ataxiaAR4543
AGLGlycogen storage diseaseAR142245
AHCYHypermethioninemia with S-adenosylhomocysteine hydrolase deficiencyAR39
ALDOAGlycogen storage diseaseAR38
AMPD1Myoadenylate deaminase deficiencyAR510
ANO5Gnathodiaphyseal dysplasia, LGMD2L and distal MMD3 muscular dystrophiesAD/AR64121
ATP2A1Brody myopathyAR1918
B3GALNT2#Muscular dystrophy-dystroglycanopathyAR1814
B4GAT1Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13AR35
C10ORF2Perrault syndrome, Mitochondrial DNA depletion syndrome, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 3AD/AR3780
CAPN3Muscular dystrophy, limb-girdle, Eosinophilic myositisAD/AR184437
CASQ1Myopathy, vacuolar, with CASQ1 aggregatesAD25
CAV3Creatine phosphokinase, elevated serum, Hypertrophic cardiomyopathy (HCM), Long QT syndrome, Muscular dystrophy, limb-girdle, type IC, Myopathy, distal, Tateyama type, Rippling muscle disease 2AD/AR2350
CHKBMuscular dystrophy, congenital, megaconialAR1127
COQ2Coenzyme Q10 deficiencyAR1631
CPT2Carnitine palmitoyltransferase II deficiencyAR72111
CTDP1Congenital cataracts, facial dysmorphism, and neuropathyAR11
DAG1Muscular dystrophy-dystroglycanopathyAR1210
DGUOKMitochondrial DNA depletion syndrome, Portal hypertension, noncirrhotic, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4AR2362
DMDBecker muscular dystrophy, Duchenne muscular dystrophy, Dilated cardiomyopathy (DCM)XL8323915
DNAJB6Muscular dystrophy, limb-girdleAD1117
DPM1Congenital disorder of glycosylationAR98
DPM2Congenital disorder of glycosylationAR22
DYSFMiyoshi muscular dystrophy, Muscular dystrophy, limb-girdle, Myopathy, distal, with anterior tibial onsetAR244529
EMDEmery-Dreifuss muscular dystrophyXL48113
ENO3Glycogen storage diseaseAR36
ETFAGlutaric aciduria, Multiple acyl-CoA dehydrogenase deficiencyAR829
ETFBGlutaric aciduria, Multiple acyl-CoA dehydrogenase deficiencyAR615
ETFDHGlutaric aciduria, Multiple acyl-CoA dehydrogenase deficiencyAR43190
FDX1LMyopathyAR12
FHL1*Myopathy with postural muscle atrophy, Emery-Dreifuss muscular dystrophy, Reducing bod myopathyXL2662
FKRPMuscular dystrophy-dystroglycanopathyAR66140
FKTNMuscular dystrophy-dystroglycanopathy, Dilated cardiomyopathy (DCM), Muscular dystrophy-dystroglycanopathy (limb-girdle)AR4558
FLAD1Lipid storage myopathy due to FLAD1 deficiency (LSMFLAD)AR910
GAAGlycogen storage diseaseAR193573
GBE1Glycogen storage diseaseAR3670
GMPPBMuscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), Limb-girdle muscular dystrophy-dystroglycanopathyAR1941
GYG1Glycogen storage disease, Polyglucosan body myopathy 2AR916
GYS1Glycogen storage diseaseAR85
HADHATrifunctional protein deficiency, Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiencyAR6571
HADHBTrifunctional protein deficiencyAR2065
ISCUMyopathy with lactic acidosisAR33
LAMA2Muscular dystrophy, congenital merosin-deficientAR199301
LAMP2Danon diseaseXL62101
LARGEMuscular dystrophy-dystroglycanopathyAR1927
LDHAGlycogen storage diseaseAR19
LPIN1Myoglobinuria, acute, recurrentAR629
MT-ATP6Neuropathy, ataxia, and retinitis pigmentosa, Leber hereditary optic neuropathy, Ataxia and polyneuropathy, adult-onset, Cardiomyopathy, infantile hypertrophic, Leigh syndrome, Striatonigral degeneration, infantile, mitochondrialMitochondrial19
MT-ATP8Cardiomyopathy, apical hypertrophic, and neuropathy, Cardiomyopathy, infantile hypertrophicMitochondrial4
MT-CO1Myoglobinuria, recurrent, Leber hereditary optic neuropathy, Sideroblastic anemia, Cytochrome C oxidase deficiency, Deafness, mitochondrialMitochondrial17
MT-CO2Cytochrome c oxidase deficiencyMitochondrial8
MT-CO3Cytochrome c oxidase deficiency, Leber hereditary optic neuropathyMitochondrial9
MT-CYBMitochondrial69
MT-ND1Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, Leber hereditary optic neuropathy, Leber optic atrophy and dystoniaMitochondrial21
MT-ND2Leber hereditary optic neuropathy, Mitochondrial complex I deficiencyMitochondrial6
MT-ND3Leber optic atrophy and dystonia, Mitochondrial complex I deficiencyMitochondrial7
MT-ND4Leber hereditary optic neuropathy, Leber optic atrophy and dystonia, Mitochondrial complex I deficiencyMitochondrial11
MT-ND4LLeber hereditary optic neuropathyMitochondrial2
MT-ND5Myoclonic epilepsy with ragged red fibers, Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, Leber hereditary optic neuropathy, Mitochondrial complex I deficiencyMitochondrial19
MT-ND6Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, Oncocytoma, Leber hereditary optic neuropathy, Leber optic atrophy and dystonia, Mitochondrial complex I deficiencyMitochondrial16
MT-RNR1Deafness, mitochondrialMitochondrial3
MT-RNR2Chloramphenicol toxicity/resistanceMitochondrial2
MT-TAMitochondrial4
MT-TCMitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodesMitochondrial3
MT-TDMitochondrial1
MT-TEDiabetes-deafness syndrome, Mitochondrial myopathy, infantile, transient, Mitochondrial myopathy with diabetesMitochondrial5
MT-TFMyoclonic epilepsy with ragged red fibers, Nephropathy, tubulointerstitial, Encephalopathy, mitochondrial, Epilepsy, mitochondrial, Myopathy, mitochondrial, Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodesMitochondrial7
MT-TGMitochondrial3
MT-THMitochondrial4
MT-TIMitochondrial7
MT-TKMyoclonic epilepsy with ragged red fibers, Leigh syndromeMitochondrial5
MT-TL1Cytochrome c oxidase deficiency, Myoclonic epilepsy with ragged red fibers, Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, Diabetes-deafness syndrome, Cyclic vomiting syndrome, SIDS, susceptibility toMitochondrial14
MT-TL2Mitochondrial multisystemic disorder, Progressive external ophthalmoplegia, Mitochondrial Myopathy, Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodesMitochondrial5
MT-TMLeigh syndrome, Mitochondrial multisystemic disorderMitochondrial1
MT-TNProgressive external ophthalmoplegia, Mitochondrial multisystemic disorderMitochondrial3
MT-TPMitochondrial2
MT-TQMitochondrial multisystemic disorderMitochondrial2
MT-TREncephalopathy, mitochondrialMitochondrial2
MT-TS1Myoclonic epilepsy with ragged red fibers, Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodesMitochondrial10
MT-TS2Mitochondrial multisystemic disorderMitochondrial2
MT-TTMitochondrial5
MT-TVHypertrophic cardiomyopathy (HCM), Leigh syndrome, Mitochondrial multisystemic disorder, Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodesMitochondrial3
MT-TWLeigh syndrome, Myopathy, mitochondrialMitochondrial8
MT-TYMitochondrial multisystemic disorderMitochondrial4
MYH3ArthrogryposisAD/AR2145
OPA1Optic atrophy, Optic atrophy 1, Optic atrophy with or without deafness, Ophthalmoplegia, myopathy, ataxia, and neuropathy, Behr synrome, Mitochondrial DNA depletion syndrome 14AD/AR96390
OPA3Optic atrophy, 3-methylglutaconic aciduriaAD/AR1315
PDSS2Coenzyme Q10 deficiencyAR84
PFKMGlycogen storage diseaseAR1226
PGAM2Glycogen storage diseaseAR411
PGK1Phosphoglycerate kinase 1 deficiencyXL1626
PGM1Congenital disorder of glycosylationAR1135
PHKA1Glycogen storage diseaseXL98
PHKBGlycogen storage diseaseAR926
PNPLA2Neutral lipid storage disease with myopathyAR1335
POLGPOLG-related ataxia neuropathy spectrum disorders, Sensory ataxia, dysarthria, and ophthalmoparesis, Alpers syndrome, Progressive external ophthalmoplegia with mitochondrial DNA deletions, Mitochondrial DNA depletion syndromeAD/AR89290
POLG2Progressive external ophthalmoplegia with mitochondrial DNA deletionsAD514
POMGNT1Muscular dystrophy-dystroglycanopathyAR9688
POMGNT2Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 8AR69
POMKCongenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type A, 12, Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type C, 12, Muscle-eye brain disease, Walker-Warburg syndromeAR68
POMT1Muscular dystrophy-dystroglycanopathyAR4796
POMT2Muscular dystrophy-dystroglycanopathyAR4573
PYGMGlycogen storage diseaseAR77168
RBCK1Polyglucosan body myopathyAR1114
RRM2BProgressive external ophthalmoplegia with mitochondrial DNA deletions, Mitochondrial DNA depletion syndromeAD/AR4141
RYR1Central core disease, Malignant hyperthermia, Minicore myopathy with external ophthalmoplegia, Centronuclear myopathy, Minicore myopathy, Multicore myopathyAD/AR241666
SCN4AHyperkalemic periodic paralysis, Myotonia, potassium-aggravated, Paramyotonia congenita, Myasthenic syndrome, congenital, Normokalemic potassium-sensitive periodic paralysisAD/AR57126
SGCAMuscular dystrophy, limb-girdleAR60100
SGCBMuscular dystrophy, limb-girdleAR3764
SGCDMuscular dystrophy, limb-girdle, Dilated cardiomyopathy (DCM)AR2127
SGCGMuscular dystrophy, limb-girdleAR3363
SIL1Marinesco-Sjogren syndromeAR1449
SLC22A5Carnitine deficiency, systemic primaryAR98151
SLC25A20Carnitine-acylcarnitine translocase deficiencyAR1542
STAC3Native American myopathy34
SUCLA2Mitochondrial DNA depletion syndromeAR929
SUCLG1Mitochondrial DNA depletion syndromeAR1228
TANGO2Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration (MECRCN)AR139
TCAPMuscular dystrophy, limb-girdle, Hypertrophic cardiomyopathy (HCM), Dilated cardiomyopathy (DCM)AD/AR1228
TK2#Mitochondrial DNA depletion syndromeAR3852
TNPO3Muscular dystrophy, limb-girdleAD35
TRIM32Bardet-Biedl syndrome, Muscular dystrophy, limb-girdleAR1316
TYMPMitochondrial DNA depletion syndromeAR8494
#

The gene has suboptimal coverage (means <90% of the gene’s target nucleotides are covered at >20x with mapping quality score (MQ>20) reads), and/or the gene has exons listed under Test limitations section that are not included in the panel as they are not sufficiently covered with high quality sequence reads.

*

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

The sensitivity to detect variants may be limited in genes marked with an asterisk (*) or number sign (#). Due to possible limitations these genes may not be available as single gene tests.

Gene refers to the HGNC approved gene symbol; Inheritance refers to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR), mitochondrial (mi), 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 Mitomap databases.

Non-coding variants covered by Metabolic Myopathy and Rhabdomyolysis Panel

To view complete table content, scroll horizontally.

GeneGenomic location HG19HGVSRefSeqRS-number
ACADMChr1:76200457c.388-19T>ANM_000016.4
ACADMChr1:76211473c.600-18G>ANM_000016.4rs370523609
ACADVLChr17:7123160c.-144_-132delCCCAGCATGCCCCinsTNM_000018.3
ACADVLChr17:7125469c.822-27C>TNM_001270447.1rs374911841
ACADVLChr17:7125485c.822-11T>GNM_001270447.1
ACADVLChr17:7126199c.1146+15C>TNM_001270447.1rs202237278
ACADVLChr17:7126948c.1252-15A>GNM_001270447.1rs765390290
ACADVLChr17:7127894c.1747+23C>TNM_001270447.1rs147546456
ADCK3Chr1:227174508c.*72dupGNM_020247.4
AGLChr1:100381954c.4260-12A>GNM_000028.2rs369973784
CAPN3Chr15:42678352c.380-13T>ANM_000070.2
CAPN3Chr15:42695919c.1746-20C>TNM_000070.2
CAPN3Chr15:42697047c.-188G>CNM_173089.1
CAPN3Chr15:42702715c.2184+21G>ANM_000070.2rs763572829
CAPN3Chr15:42702770c.2185-16A>GNM_000070.2
DGUOKChr2:74177650c.444-62C>ANM_080916.2
DGUOKChr2:74177701c.444-11C>GNM_080916.2rs536746349
DMDChrX:31165653c.10554-18C>GNM_004006.2
DMDChrX:31200680c.9974+175T>ANM_004006.2
DMDChrX:31224814c.9564-30A>TNM_004006.2
DMDChrX:31225211c.9564-427T>GNM_004006.2
DMDChrX:31226400c.9563+1215A>GNM_004006.2
DMDChrX:31229031c.9362-1215A>GNM_004006.2
DMDChrX:31241047c.9361+117A>GNM_004006.2
DMDChrX:31279293c.9225-160A>GNM_004006.2
DMDChrX:31279418c.9225-285A>GNM_004006.2
DMDChrX:31279420c.9225-287C>ANM_004006.2
DMDChrX:31279780c.9225-647A>GNM_004006.2rs398124091
DMDChrX:31279781c.9225-648A>GNM_004006.2rs398124084
DMDChrX:31332523c.9224+9192C>ANM_004006.2
DMDChrX:31382270c.9085-15519G>TNM_004006.2
DMDChrX:31613687c.8217+32103G>TNM_004006.2
DMDChrX:31627738c.8217+18052A>GNM_004006.2
DMDChrX:31697714c.7661-11T>CNM_004006.2
DMDChrX:31897527c.6913-4037T>GNM_004006.2
DMDChrX:31983146c.6614+3310G>TNM_004006.2rs797045526
DMDChrX:32274692c.6290+30954C>TNM_004006.2
DMDChrX:32305833c.6118-15A>GNM_004006.2
DMDChrX:32360414c.5740-15G>TNM_004006.2
DMDChrX:32366860c.5326-215T>GNM_004006.2
DMDChrX:32379144c.5325+1743_5325+1760delTATTAAAAAATGGGTAGANM_004006.2
DMDChrX:32398808c.4675-11A>GNM_004006.2
DMDChrX:32460274c.3787-843C>ANM_004006.2
DMDChrX:32470726c.3603+2053G>CNM_004006.2
DMDChrX:32479316c.3432+2240A>GNM_004006.2
DMDChrX:32479520c.3432+2036A>GNM_004006.2
DMDChrX:32669100c.961-5831C>TNM_004006.2rs398124099
DMDChrX:32669194c.961-5925A>CNM_004006.2
DMDChrX:32716130c.832-15A>GNM_004006.2rs72470513
DMDChrX:32756908c.650-39498A>GNM_004006.2
DMDChrX:32827744c.531-16T>A/GNM_004006.2
DMDChrX:32827744c.531-16T>ANM_004006.2
DMDChrX:32827744c.531-16T>GNM_004006.2
DMDChrX:32841967c.265-463A>GNM_004006.2
DMDChrX:33032666c.93+5590T>ANM_004006.2
DMDChrX:33192452c.31+36947G>ANM_004006.2
DMDChrX:33229483c.-54T>ANM_004006.2
DYSFChr2:71817308c.3443-33A>GNM_003494.3rs786205083
DYSFChr2:71840553c.4410+13T>GNM_003494.3
DYSFChr2:71889030c.4886+1249G>TNM_003494.3
DYSFChr2:71900503c.5668-824C>TNM_003494.3
DYSFChr2:71913729c.*107T>ANM_003494.3rs11903223
EMDChrX:153608559c.266-27_266-10delTCTGCTACCGCTGCCCCCNM_000117.2
ETFDHChr4:159593534c.-75A>GNM_004453.2
ETFDHChr4:159602711c.176-636C>GNM_004453.2
FKRPChr19:47249328c.-272G>ANM_024301.4
FKTNChr9:108368857c.648-1243G>TNM_006731.2
GAAChr17:78078341c.-32-13T>GNM_000152.3rs386834236
GAAChr17:78078341c.-32-13T>ANM_000152.3
GAAChr17:78078351c.-32-3C>A/GNM_000152.3
GAAChr17:78078352c.-32-2A>GNM_000152.3
GAAChr17:78078353c.-32-1G>CNM_000152.3
GAAChr17:78078369c.-17C>TNM_000152.3
GAAChr17:78082266c.1076-22T>GNM_000152.3rs762260678
GAAChr17:78090422c.2190-345A>GNM_000152.3
GAAChr17:78092432c.2647-20T>GNM_000152.3
GBE1Chr3:81542964c.2053-3358_2053-3350delGTGTGGTGGinsTGTTTTTTACATGACAGGTNM_000158.3rs869320698
GMPPBChr3:49761246c.-87C>TNM_013334.3rs780961444
GYG1Chr3:148717967c.481+3276C>GNM_004130.3
HADHBChr2:26500642c.442+614A>GNM_000183.2
HADHBChr2:26500691c.442+663A>GNM_000183.2
ISCUChr12:108961426c.418+382G>CNM_213595.2rs767000507
LAMA2Chr6:129633984c.3175-22G>ANM_000426.3rs777129293
LAMA2Chr6:129636608c.3556-13T>ANM_000426.3rs775278003
LAMA2Chr6:129714172c.5235-18G>ANM_000426.3rs188365084
LAMA2Chr6:129835506c.8989-12C>GNM_000426.3rs144860334
OPA1Chr3:193334932c.449-34dupANM_130837.2
OPA1Chr3:193374829c.2179-40G>CNM_130837.2
PFKMChr12:48535459c.1626-64A>GNM_001166686.1
PGK1ChrX:77381262c.1214-25T>GNM_000291.3
PGM1Chr1:64113966c.1199-222G>TNM_001172818.1
POMT1Chr9:134379574c.-30-2A>GNM_007171.3
POMT2Chr14:77751989c.1333-14G>ANM_013382.5
PYGMChr11:64523631c.661-601G>ANM_005609.2
PYGMChr11:64525847c.425-26A>GNM_005609.2rs764313717
RYR1Chr19:38997317c.8692+131G>ANM_000540.2
RYR1Chr19:39074134c.14647-1449A>GNM_000540.2rs193922886
SGCAChr17:48246419c.585-31_585-23delTCTGCTGACNM_000023.2
SGCAChr17:48246421c.585-31_585-24delTCTGCTGANM_000023.2
SGCAChr17:48247492c.748-12_748-11delCTinsAANM_000023.2
SGCGChr13:23755086c.-127_-121delACAGTTGNM_000231.2rs1422849467
SGCGChr13:23755215c.-1+1G>TNM_000231.2
SIL1Chr5:138283180c.1030-18G>ANM_022464.4rs769052639
SLC22A5Chr5:131714054c.394-16T>ANM_003060.3rs775097754
SLC22A5Chr5:131722665c.825-52G>ANM_003060.3

Test Strengths

The strengths of this test include:

  • CAP 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
  • Some of the panels include the whole mitochondrial genome (please see the Panel Content section)
  • Our Nucleus online portal providing transparent and easy access to quality and performance data at the patient level
  • ~2,000 non-coding disease causing variants in our clinical grade NGS assay for panels (please see ‘Non-coding disease causing variants covered by this panel’ in the Panel Content section)
  • 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: *B3GALNT2* (NM_001277155:2), *TK2* (NM_001271934:3). 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
  • Some of the panels include the whole mitochondrial genome but not all (please see the Panel Content section)
  • 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 in nuclear genes (variant with a minor allele fraction of 14.6% is detected with 90% probability)
  • Stretches of mononucleotide repeats
  • Low level heteroplasmy in mtDNA (>90% are detected at 5% level)
  • Indels larger than 50bp
  • Single exon deletions or duplications
  • Variants within pseudogene regions/duplicated segments
  • Some disease causing variants present in mtDNA are not detectable from blood, thus post-mitotic tissue such as skeletal muscle may be required for establishing molecular diagnosis.

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.

The genes on the panel have been carefully selected based on scientific literature, mutation databases and our experience.

Our panels are sectioned from our high-quality, clinical grade NGS assay. Please see our sequencing and detection performance table for details regarding our ability to detect different types of alterations (Table).

Assays have been validated for various sample types including EDTA-blood, isolated DNA (excluding from formalin fixed paraffin embedded tissue), saliva and dry blood spots (filter cards). These sample types were selected in order to maximize the likelihood for high-quality DNA yield. The diagnostic yield varies depending on the assay used, referring healthcare professional, hospital and country. Plus analysis increases the likelihood of finding a genetic diagnosis for your patient, as large deletions and duplications cannot be detected using sequence analysis alone. Blueprint Genetics’ Plus Analysis is a combination of both sequencing and deletion/duplication (copy number variant (CNV)) analysis.

The performance metrics listed below are from an initial validation performed at our main laboratory in Finland. The performance metrics of our laboratory in Marlborough, MA, are equivalent.

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

Sensitivity % (TP/(TP+FN)Specificity %
Single nucleotide variants99.89% (99,153/99,266)>99.9999%
Insertions, deletions and indels by sequence analysis
1-10 bps99.2% (7,745/7,806)>99.9999%
11-50 bps99.13% (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/duplication98.7%100.00%
Microdeletion/-duplication sdrs (large CNVs, n=37))
Size range (0.1-47 Mb)100% (25/25)
   
The performance presented above reached by Blueprint Genetics high-quality, clinical grade NGS sequencing assay with the following coverage metrics
   
Mean sequencing depth143X
Nucleotides with >20x sequencing coverage (%)99.86%

Performance of Blueprint Genetics Mitochondrial Sequencing Assay.

Sensitivity %Specificity %
ANALYTIC VALIDATION (NA samples; n=4)
Single nucleotide variants
Heteroplasmic (45-100%)100.0% (50/50)100.0%
Heteroplasmic (35-45%)100.0% (87/87)100.0%
Heteroplasmic (25-35%)100.0% (73/73)100.0%
Heteroplasmic (15-25%)100.0% (77/77)100.0%
Heteroplasmic (10-15%)100.0% (74/74)100.0%
Heteroplasmic (5-10%)100.0% (3/3)100.0%
Heteroplasmic (<5%)50.0% (2/4)100.0%
CLINICAL VALIDATION (n=76 samples)
All types
Single nucleotide variants n=2026 SNVs
Heteroplasmic (45-100%)100.0% (1940/1940)100.0%
Heteroplasmic (35-45%)100.0% (4/4)100.0%
Heteroplasmic (25-35%)100.0% (3/3)100.0%
Heteroplasmic (15-25%)100.0% (3/3)100.0%
Heteroplasmic (10-15%)100.0% (9/9)100.0%
Heteroplasmic (5-10%)92.3% (12/13)99.98%
Heteroplasmic (<5%)88.9% (48/54)99.93%
Insertions and deletions by sequence analysis n=40 indels
Heteroplasmic (45-100%) 1-10bp100.0% (32/32)100.0%
Heteroplasmic (5-45%) 1-10bp100.0% (3/3)100.0%
Heteroplasmic (<5%) 1-10bp100.0% (5/5)99,997%
SIMULATION DATA /(mitomap mutations)
Insertions, and deletions 1-24 bps by sequence analysis; n=17
Homoplasmic (100%) 1-24bp100.0% (17/17)99.98%
Heteroplasmic (50%)100.0% (17/17)99.99%
Heteroplasmic (25%)100.0% (17/17)100.0%
Heteroplasmic (20%)100.0% (17/17)100.0%
Heteroplasmic (15%)100.0% (17/17)100.0%
Heteroplasmic (10%)94.1% (16/17)100.0%
Heteroplasmic (5%)94.1% (16/17)100.0%
Copy number variants (separate artifical mutations; n=1500)
Homoplasmic (100%) 500 bp, 1kb, 5 kb100.0%100.0%
Heteroplasmic (50%) 500 bp, 1kb, 5 kb100.0%100.0%
Heteroplasmic (30%) 500 bp, 1kb, 5 kb100.0%100.0%
Heteroplasmic (20%) 500 bp, 1kb, 5 kb99.7%100.0%
Heteroplasmic (10%) 500 bp, 1kb, 5 kb99.0%100.0%
The performance presented above reached by following coverage metrics at assay level (n=66)
Mean of mediansMedian of medians
Mean sequencing depth MQ0 (clinical)18224X17366X
Nucleotides with >1000x MQ0 sequencing coverage (%) (clinical)100%
rho zero cell line (=no mtDNA), mean sequencing depth12X

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. If the test includes the mitochondrial genome the target region gene list contains the mitochondrial genes. 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 suboptimal coverage (<20X for nuclear genes and <1000X for mtDNA) if applicable. This reflects our mission to build fully transparent diagnostics where ordering providers can easily visualize the crucial details of the analysis process.

We provide customers with comprehensive clinical report available on the market. Clinical interpretation requires a fundamental understanding of clinical genetics and genetic principles. At Blueprint Genetics, our Ph.D. molecular geneticists, medical professionals, and other highly experienced experts prepare clinical reports by evaluating the identified variants in the context of the phenotypic information provided in the requisition form.

Our goal is to provide clinically meaningful reports that are understandable for all medical professionals regardless of whether they have formal training in genetics. Variant classification is the cornerstone of clinical interpretation and resulting patient management decisions. Our classifications follow the ACMG guideline 2015. Sequence and copy number variants classified as pathogenic, likely pathogenic, and variants of uncertain significance (VUS) are confirmed using bidirectional Sanger sequencing or by orthogonal methods such as qPCR/ddPCR when they do not meet our stringent NGS quality metrics for a true positive call.

Our clinical report includes tables for sequence and copy number variants that include basic variant information (genomic coordinates, HGVS nomenclature, zygosity, allele frequencies, in silico predictions, 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 panel report is divided into primary findings and additional findings sections. Variants reported as primary findings are known disease-causing variants or rare variants that could potentially explain the patient’s phenotype as described to the laboratory at the time of interpretation. The conclusion summarizes all the existing information and provides our rationale for the classification of the variant.

Variants reported as additional findings are variants that are not likely or sufficient to cause the tested patient’s phenotype, based on the current knowledge. Additional findings in panel reports include variants that are, for example, carrierships of single heterozygous variants in genes associated with autosomal recessive disorders, variants of uncertain significance in genes associated with autosomal dominant disorders (if pathogenic or likely pathogenic variants considered sufficient to explain the patient’s phenotype are reported as primary findings), or risk alleles identified in genes included in the panel.

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 reclassify previously reported variants as new information becomes available. If a variant previously reported as a primary or secondary finding by Blueprint Genetics is reclassified so that it becomes diagnostic (VUS to P/LP) or earlier molecular diagnosis is removed (P/LP to VUS, LB, B), our laboratory will issue a follow-up statement to the original ordering healthcare provider at no additional cost.