Comprehensive Metabolism Panel

Last modified: Jun 12, 2018


  • Is a 434 gene panel that includes assessment of non-coding variants
  • Is ideal for patients with a clinical suspicion of an inborn error of metabolism.

Analysis methods

  • PLUS
  • SEQ


4 weeks

Number of genes


Test code


Panel size


CPT codes

SEQ 81406
SEQ 81407
SEQ 81408
DEL/DUP 81479


The Blueprint Genetics Comprehensive Metabolism Panel (test code ME0701):

  • Is a 434 gene panel that includes assessment of selected non-coding disease-causing variants
  • All exons of the GBA gene have segmentally duplicated pseudogenes that reduce sensitivity of NGS diagnostics in general. However, Blueprint Genetics custom assay has good coverage (>20x) with high mapping rates (mapping quality >40) for 100.0% of the target regions in GBA gene. Our validation showed high mean coverage of 184X for the GBA gene. Thus, our NGS Panel is not expected to have major limitations in detecting variants in GBA gene although clinical validation has not been performed at large scale for Gaucher disease.

  • Is available as PLUS analysis (sequencing analysis and deletion/duplication analysis), sequencing analysis only or deletion/duplication analysis only

Test Specific Strength

All exons of the GBA gene have segmentally duplicated pseudogenes that reduce sensitivity of NGS diagnostics in general. However, Blueprint Genetics custom assay has good coverage (>20x) with high mapping rates (mapping quality >40) for 100.0% of the target regions in GBA gene. Our validation showed high mean coverage of 184X for the GBA gene. Thus, our NGS Panel is not expected to have major limitations in detecting variants in GBA gene although clinical validation has not been performed at large scale for Gaucher disease.

ICD codes

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

ICD-10 Disease
Z13.228 Inborn error of metabolism

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.

Metabolic disorders often have similar and overlapping symptoms. They may be difficult to subtype without definitive information on the causative mutations and genes. This panel includes well over 400 genes – comprehensive enough to cover the majority of known monogenic metabolic syndromes, deficiencies and diseases. Most phenotypes covered by this panel result from mutations making specific enzymes defective in metabolic pathways. This often results in the accumulation of toxic intermediate products or the loss of specific end products required in metabolic pathways. Additionally, conditions covered by this panel include those with an imbalance in using, storing or converting energy. Most inherited metabolic disorders are quite rare. However, the combined prevalence is estimated at 1:1,000 or 1:2000 newborns. Some specific populations, where the genetic heterogeneity is smaller, may even have much higher numbers.

Genes in the Comprehensive Metabolism Panel and their clinical significance

Gene Associated phenotypes Inheritance ClinVar HGMD
ABCC8 Hyperinsulinemic hypoglycemia, Diabetes, permanent neonatal, Hypoglycemia, leucine-induced, Diabetes mellitus, transient neonatal AD/AR 128 621
ABCD1* Adrenoleukodystrophy XL 83 659
ABCD3 Zellweger syndrome AR 1 3
ABCD4 Methylmalonic aciduria and homocystinuria AR 5 7
ACAD8 Isobutyryl-CoA dehydrogenase deficiency AR 13 21
ACAD9 Acyl-CoA dehydrogenase family, deficiency AR 25 44
ACADL Long chain acyl-CoA dehydrogenase deficiency AD/AR 1
ACADM Acyl-CoA dehydrogenase, medium chain, deficiency AR 89 167
ACADS Acyl-CoA dehydrogenase, short-chain, deficiency AR 51 81
ACADSB 2-methylbutyryl-CoA dehydrogenase deficiency AR 7 12
ACADVL Acyl-CoA dehydrogenase, very long chain, deficiency AR 94 270
ACAT1 Alpha-methylacetoacetic aciduria AR 30 91
ACOX1 Peroxisomal acyl-CoA oxidase deficiency AR 13 26
ACSF3 Combined malonic and methylmalonic aciduria AR 19 19
ACY1 Aminoacylase 1 deficiency AR 5 14
ADA Severe combined immunodeficiency due to adenosine deaminase deficiency AR 39 88
ADAMTSL2*,# Geleophysic dysplasia AR 8 28
ADAR Dyschromatosis symmetrica hereditaria, Aicardi-Goutières syndrome AD/AR 24 211
ADCK3 Coenzyme Q10 deficiency, Progressive cerebellar ataxia and atrophy, Spinocerebellar ataxia AR 44 39
ADK Hypermethioninemia due to adenosine kinase deficiency AD 6 14
ADSL Adenylosuccinase deficiency AR 24 56
AGA Aspartylglucosaminuria AR 41 37
AGK* Sengers syndrome, Cataract 38 AR 18 27
AGL Glycogen storage disease AR 90 243
AGPAT2 Lipodystrophy, congenital generalized AR 25 39
AGPS Rhizomelic chondrodysplasia punctata type 3 AR 4 8
AGXT Hyperoxaluria AR 180 202
AHCY Hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency AR 3 9
AKT2 Hypoinsulinemic hypoglycemia with hemihypertrophy AD 4 3
ALAD Porphyria, acute hepatic AR 6 11
ALAS2 Anemia, sideroblastic, Protoporphyria, erythropoietic XL 27 98
ALDH5A1 Succinic semialdehyde dehydrogenase deficiency AR 14 69
ALDH7A1 Epilepsy, pyridoxine-dependent AR 50 113
ALDOA Glycogen storage disease AR 2 8
ALDOB Fructose intolerance, hereditary AR 32 66
ALG1* Congenital disorder of glycosylation AR 23 43
ALG2 Congenital disorder of glycosylation, Myasthenic syndrome, congenital AR 4 5
ALG3 Congenital disorder of glycosylation AR 9 17
ALG6 Congenital disorder of glycosylation AR 8 24
ALG8 Congenital disorder of glycosylation AR 10 17
ALG9 Congenital disorder of glycosylation, Gillessen-Kaesbach-Nishimura syndrome AR 4 4
ALG11* Congenital disorder of glycosylation AR 11 14
ALG12 Congenital disorder of glycosylation AR 10 15
ALG13 Congenital disorder of glycosylation XL 5 9
AMACR Alpha-methylacyl-CoA racemase deficiency, Bile acid synthesis defect AR 3 8
AMN Megaloblastic anemia-1, Norwegian AR 26 33
AMPD1 Myoadenylate deaminase deficiency AR 5 9
AMT Glycine encephalopathy AR 25 95
ANO5 Gnathodiaphyseal dysplasia, LGMD2L and distal MMD3 muscular dystrophies AD/AR 60 115
ANO10 Spinocerebellar ataxia AR 18 16
ANTXR2 Hyalinosis, infantile systemic, Fibromatosis, juveline hyaline AR 16 45
APRT Adenine phosphoribosyltransferase deficiency AR 11 47
APTX Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia AR 14 42
ARG1 Hyperargininemia AR 17 54
ARSA Metachromatic leukodystrophy AR 96 223
ARSB Mucopolysaccharidosis (Maroteaux-Lamy) AR 27 199
ASAH1 Spinal muscular atrophy with progressive myoclonic epilepsy, Farber lipogranulomatosis AR 13 71
ASL Argininosuccinic aciduria AR 38 154
ASPA Aspartoacylase deficiency (Canavan disease) AR 39 102
ASS1 Citrullinemia AR 53 153
ATIC AICAR transformylase/IMP cyclohydrolase deficiency AR 2 4
ATP6V0A2 Cutis laxa, Wrinkly skin syndrome AR 16 54
ATP7B Wilson disease AR 146 884
ATP13A2 Parkinson disease (Kufor-Rakeb syndrome) AR 20 37
AUH 3-methylglutaconic aciduria AR 13 11
B3GLCT Peters-plus syndrome AR 9 15
B4GALT1 Congenital disorder of glycosylation AR 1 2
BCKDHA Maple syrup urine disease AR 46 91
BCKDHB Maple syrup urine disease AR 69 94
BCS1L Bjornstad syndrome, GRACILE syndrome, Leigh syndrome, Mitochondrial complex III deficiency, nuclear type 1 AR 33 37
BOLA3 Multiple mitochondrial dysfunctions syndrome 2 AR 3 5
BSCL2 Lipodystrophy, congenital generalized, Encephalopathy, progressive, Neuropathy, distal hereditary motor, type VA, Charcot-Marie-Tooth disease type 2, Silver syndrome, Silver spastic paraplegia syndrome, Spastic paraplegia 17 AR 32 47
BSND Sensorineural deafness with mild renal dysfunction, Bartter syndrome AR 10 19
BTD Biotinidase deficiency AR 180 236
C10ORF2 Perrault syndrome, Mitochondrial DNA depletion syndrome, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 3 AR 36 77
C12ORF65 Spastic paraplegia, Combined oxidative phosphorylation deficiency AR 10 11
CACNA1S Hypokalemic periodic paralysis, Malignant hyperthermia, Thyrotoxic periodic paralysis AD 8 41
CASR Hypocalcemia, Neonatal hyperparathyroidism, Familial Hypocalciuric hypercalcemia with transient Neonatal hyperparathyroidism AD/AR 103 393
CAV1 Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome, Lipodystrophy, congenital generalized, Pulmonary hypertension, primary 3 AD/AR 7 9
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
CBS Homocystinuria due to cystathionine beta-synthase deficiency AR 72 187
CD320 Methylmalonic aciduria due to transcobalamin receptor defect AR 1
CLCN1 Myotonia congenita, Myotonia congenita, Myotonia levior AD/AR 77 297
CLCNKB* Bartter syndrome AR/Digenic 19 102
CLDN16 Hypomagnesemia, renal AR 18 61
CLDN19 Hypomagnesemia, renal AR 3 19
CLN3 Neuronal ceroid lipofuscinosis, type 3 AR 87 71
CLN5 Neuronal ceroid lipofuscinosis, type 5 AR 49 45
CLN6 Neuronal ceroid lipofuscinosis, type 6 AR 29 82
CLN8 Neuronal ceroid lipofuscinosis, type 8 AR 35 42
CLPB 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia (MEGCANN) AR 25 25
CNNM2 Hypomagnesemia, renal, Hypomagnesemia, seizures, and mental retardation AR 5 6
CNNM4 Jalili syndrome AR 10 23
COG1 Congenital disorder of glycosylation AR 4 2
COG4 Congenital disorder of glycosylation AR 9 4
COG5 Congenital disorder of glycosylation AR 3 10
COG6 Congenital disorder of glycosylation, Shaheen syndrome AR 9 9
COG7 Congenital disorder of glycosylation AR 5 5
COG8 Congenital disorder of glycosylation AR 5 7
COL2A1 Avascular necrosis of femoral head, Rhegmatogenous retinal detachment, Epiphyseal dysplasia, with myopia and deafness, Czech dysplasia, Achondrogenesis type 2, Platyspondylic dysplasia Torrance type, Hypochondrogenesis, Spondyloepiphyseal dysplasia congenital (SEDC), Spondyloepimetaphyseal dysplasia (SEMD) Strudwick type, Kniest dysplasia, Spondyloperipheral dysplasia, Mild SED with premature onset arthrosis, SED with metatarsal shortening, Stickler syndrome type 1 AD 166 544
COL11A2 Weissenbacher-Zweymuller syndrome, Deafness, Otospondylomegaepiphyseal dysplasia, Fibrochondrogenesis, Stickler syndrome type 3 (non-ocular) AD/AR 28 55
COQ2 Coenzyme Q10 deficiency AR 16 31
COQ4 Coenzyme Q10 deficiency 7 AR 16 13
COQ5 Coenzyme Q10 deficiency AR 1 2
COQ6 Coenzyme Q10 deficiency AR 14 15
COQ7 Coenzyme Q10 deficiency, primary 8 AR 1 2
COQ9 Coenzyme Q10 deficiency AR 2 3
CPOX Coproporphyria, Harderoporphyria AD/AR 15 69
CPS1 Carbamoylphosphate synthetase I deficiency AR 23 261
CPT1A Carnitine palmitoyltransferase deficiency AR 49 48
CPT2 Carnitine palmitoyltransferase II deficiency AR 48 107
CTH Cystathioninuria AR 5 9
CTNS Cystinosis AR 55 146
CTSA Galactosialidosis AR 17 36
CTSC Periodontitis, juvenile, Haim-Munk syndrome, Papillon-Lefevre syndrome AR 16 92
CTSD Ceroid lipofuscinosis, neuronal AR 12 18
CTSK Pycnodysostosis AR 25 54
CUBN* Megaloblastic anemia-1, Finnish AR 37 52
D2HGDH D-2-hydroxyglutaric aciduria 1 AR 10 32
DBT Maple syrup urine disease AR 32 72
DDOST Congenital disorder of glycosylation AR 3 2
DGUOK Mitochondrial DNA depletion syndrome, Portal hypertension, noncirrhotic, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4 AR 23 62
DHCR7 Smith-Lemli-Opitz syndrome AR 67 216
DHDDS Retinitis pigmentosa AR 4 7
DHODH Postaxial acrofacial dysostosis (Miller syndrome) AR 8 20
DLD Dihydrolipoyl dehydrogenase deficiency AR 24 21
DNM1L Encephalopathy due to defective mitochondrial and peroxisomal fission 1 AD 18 20
DOLK Congenital disorder of glycosylation AR 8 11
DPAGT1 Congenital disorder of glycosylation, Myasthenic syndrome, congenital AR 17 30
DPM1 Congenital disorder of glycosylation AR 8 8
DPM2 Congenital disorder of glycosylation AR 2 2
DPM3 Congenital disorder of glycosylation AR 2 2
DPYD 5-fluorouracil toxicity, Epilepsy, hearing loss, and mental retardation syndrome; EHLMRS AD/AR 54 85
DPYS Dihydropyriminidase deficiency AR 8 29
DYM Dyggve-Melchior-Clausen dysplasia, Smith-McCort dysplasia AR 21 34
DYSF Miyoshi muscular dystrophy, Muscular dystrophy, limb-girdle, Myopathy, distal, with anterior tibial onset AR 188 517
EBP Chondrodysplasia punctata, Male EBP disorder with neurologic defects (MEND) XL 43 90
ECHS1 Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency AR 23 31
EGF Hypomagnesemia, renal AR 1 2
ENO3 Glycogen storage disease AR 3 5
EPM2A Epilepsy, progressive myoclonic AR 16 76
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
FAH Tyrosinemia AR 39 101
FAM111A Kenny-Caffey syndrome, type 2 AD 4 9
FBP1 Fructose-1,6-bisphosphatase deficiency AR 18 42
FBXL4 Mitochondrial DNA depletion syndrome AR 55 47
FECH Protoporphyria, erythropoietic AD/AR 14 193
FH Hereditary leiomyomatosis and renal cell cancer AD/AR 156 205
FKRP Muscular dystrophy-dystroglycanopathy AR 41 137
FKTN Muscular dystrophy-dystroglycanopathy, Dilated cardiomyopathy (DCM), Muscular dystrophy-dystroglycanopathy (limb-girdle) AD/AR 34 57
FLAD1 Lipid storage myopathy due to FLAD1 deficiency (LSMFLAD) AR 9 10
FLNA Frontometaphyseal dysplasia, Osteodysplasty Melnick-Needles, Otopalatodigital syndrome type 1, Otopalatodigital syndrome type 2, Terminal osseous dysplasia with pigmentary defects XL 119 235
FLNB Larsen syndrome (dominant), Atelosteogenesis type 1, Atelosteogenesis type 3, Spondylo-carpal-tarsal dyspasia AD/AR 41 103
FMO3 Trimethylaminuria AR 19 53
FOLR1 Cerebral folate deficiency AR 10 27
FOXRED1 Leigh syndrome, Mitochondrial complex I deficiency AR 15 8
FUCA1 Fucosidosis AR 19 32
FXYD2 Hypomagnesemia, renal AD 1 1
G6PC Glycogen storage disease AR 35 115
GAA Glycogen storage disease AR 147 558
GALC Krabbe disease AR 74 234
GALE Galactose epimerase deficiency AR 13 25
GALK1 Galactokinase deficiency AR 5 44
GALNS Mucopolysaccharidosis (Morquio syndrome) AR 48 334
GALT Galactosemia AR 248 327
GAMT Guanidinoacetate methyltransferase deficiency AR 18 58
GATM Arginine:glycine amidinotransferase deficiency AR 6 16
GBA* Gaucher disease AR 84 471
GBE1 Glycogen storage disease AR 34 70
GCDH Glutaric aciduria AR 70 208
GCH1 Dopa-Responsive Dystonia Hyperphenylalaninemia, BH4-deficient, GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia AD/AR 39 236
GCK Hyperinsulinemic hypoglycemia, familial, Diabetes mellitus, permanent neonatal, Maturity-onset diabetes of the young, type 2 AD/AR 179 825
GCSH Glycine encephalopathy AR 4 2
GFM1 Combined oxidative phosphorylation deficiency AR 18 18
GIF Intrinsic factor deficiency AR 7 20
GLA Fabry disease XL 215 919
GLB1 GM1-gangliosidosis, Mucopolysaccharidosis (Morquio syndrome) AR 65 212
GLDC Glycine encephalopathy AR 105 424
GLRX5 Spasticity, childhood-onset, with hyperglycinemia AR 5 6
GLUD1* Hyperammonemia-hyperinsulinism, Hyperinsulinemic hypoglycemia AD/AR 14 38
GLUL Glutamine deficiency, congenital AR 4 3
GM2A GM2-gangliosidosis, AB variant AR 9 10
GMPPA Alacrima, achalasia, and mental retardation syndrome AR 6 11
GNE Inclusion body myopathy, Nonaka myopathy, Sialuria AD/AR 58 201
GNMT Glycine N-methyltransferase deficiency AR 3 5
GNPAT Rhizomelic chondrodysplasia punctata, rhizomelic AR 8 14
GNPTAB Mucolipidosis AR 155 183
GNPTG Mucolipidosis AR 28 45
GNS Mucopolysaccharidosis (Sanfilippo syndrome) AR 7 25
GPC3 Simpson-Golabi-Behmel syndrome XL 29 72
GPHN Hyperekplexia, Molybdenum cofactor deficiency AD/AR 29 20
GUSB* Mucopolysaccharidosis AR 26 61
GYG1 Glycogen storage disease, Polyglucosan body myopathy 2 AR 8 15
GYS1 Glycogen storage disease AR 6 5
GYS2 Glycogen storage disease AR 15 22
HADH 3-hydroxyacyl-CoA dehydrogenase deficiency AR 10 26
HADHA Trifunctional protein deficiency, Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency AR 50 70
HADHB Trifunctional protein deficiency AR 18 60
HAMP Hemochromatosis AR 5 15
HCFC1 Combined methylmalonic acidemia and hyperhomocysteinemia XL 9 16
HEXA Tay-Sachs disease, GM2-gangliosidosis, Hexosaminidase A deficiency AR 112 184
HEXB Sandhoff disease AR 34 111
HFE Hemochromatosis AR/Digenic 10 56
HFE2 Hemochromatosis AR 16 51
HGD Alkaptonuria AR 42 136
HGSNAT Mucopolysaccharidosis (Sanfilippo syndrome), Retinitis pigmentosa AR 24 70
HIBCH 3-hydroxyisobutryl-CoA hydrolase deficiency AR 19 13
HLCS Holocarboxylase synthetase deficiency AR 22 47
HMBS Porphyria, acute intermittent, Hydroxymethylbilane synthase deficiency AD/AR 53 416
HMGCL 3-hydroxy-3-methylglutaryl-CoA lyase deficiency AR 13 60
HMGCS2 3-hydroxy-3-methylglutaryl-CoA synthase 2 deficiency AR 11 27
HNF1A Maturity onset diabetes of the young, Renal cell carcinoma, nonpapillary clear cell, Liver adenomatosis AD 72 524
HNF1B Renal cell carcinoma, nonpapillary chromophobe, Renal cysts and diabetes syndrome AD 34 227
HNF4A Congenital hyperinsulinism, diazoxide-responsive, Maturity onset diabetes of the young, Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young AD 30 147
HPD Hawksinuria, Tyrosinemia AD/AR 3 9
HPRT1 Lesch-Nyhan syndrome, Kelley-Seegmiller syndrome XL 69 426
HRAS Costello syndrome, Congenital myopathy with excess of muscle spindles AD 41 29
HSD17B4 Perrault syndrome, D-bifunctional protein deficiency AR 45 99
HSD17B10 17-beta-hydroxysteroid dehydrogenase X deficiency, Mental retardation, syndromic XL 10 14
HYAL1 Mucopolysaccharidosis AR 2 3
IDH2 D-2-hydroxyglutaric aciduria 2 AD 10 3
IDS* Mucopolysaccharidosis XL 80 631
IDUA Mucopolysaccharidosis AR 57 274
IFIH1 Singleton-Merten syndrome, Aicardi-Goutieres syndrome 7 AD 13 17
INSR Hyperinsulinemic hypoglycemia, familial, Rabson-Mendenhall syndrome, Donohoe syndrome AD/AR 44 183
ISCU Myopathy with lactic acidosis AR 3 3
IVD Isovaleric acidemia AR 39 87
KCNA1 Episodic ataxia/myokymia syndrome AD 24 41
KCNJ2 Short QT syndrome, Andersen syndrome, Long QT syndrome, Atrial fibrillation AD 41 87
KCNJ10 Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SESAME syndrome), Pendred syndrome, Enlarged vestibular aqueduct AR/Digenic 14 25
KCNJ11 Hyperinsulinemic hypoglycemia, Diabetes, permanent neonatal, Diabetes mellitus, transient neonatal, Maturity-onset diabetes of the young 13, Paternally-inherited mutations can cause Focal adenomatous hyperplasia AD/AR 56 173
L2HGDH L-2-hydroxyglutaric aciduria AR 13 76
LAMA2 Muscular dystrophy, congenital merosin-deficient AR 125 294
LAMP2 Danon disease XL 57 97
LCT Lactase deficiency AR 11 14
LDB3 Dilated cardiomyopathy (DCM), Myopathy, myofibrillar AD 9 14
LDHA Glycogen storage disease AR 1 9
LIAS Pyruvate dehydrogensae lipoic acid synthetase deficiency AR 9 5
LIPA Wolman disease, Cholesterol ester storage disease AR 13 84
LIPE Abdominal obesity-metabolic syndrome 4 AR 3 4
LIPT1 Lipoyltransferase 1 deficiency AR 8 8
LMBRD1 Methylmalonic aciduria and homocystinuria AR 4 9
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
LPIN1 Myoglobinuria, acute, recurrent AR 6 29
MAGT1 Immunodeficiency, with magnesium defect, Epstein-Barr virus infection and neoplasia, Mental retardation, X-linked 95 XL 5 14
MAN1B1 Mental retardation AR 8 25
MAN2B1 Mannosidosis, alpha B, lysosomal AR 37 144
MANBA Mannosidosis, lysosomal AR 12 18
MCCC1 3-Methylcrotonyl-CoA carboxylase 1 deficiency AR 34 103
MCCC2 3-Methylcrotonyl-CoA carboxylase 2 deficiency AR 22 113
MCEE Methylmalonyl-CoA epimerase deficiency AR 1 4
MCOLN1 Mucolipidosis AR 46 35
MFN2 Hereditary motor and sensory neuropathy, Charcot-Marie-Tooth disease AD/AR 59 220
MFSD8 Ceroid lipofuscinosis, neuronal AR 25 46
MGAT2 Congenital disorder of glycosylation AR 6 5
MLYCD Malonyl-CoA decarboxylase deficiency AR 13 38
MMAA Methylmalonic acidemia AR 46 74
MMAB Methylmalonic acidemia AR 23 39
MMACHC Methylmalonic aciduria and homocystinuria AR 30 93
MMADHC Methylmalonic aciduria and homocystinuria AR 16 13
MOCOS Xanthinuria, type II AR 4 4
MOCS1* Molybdenum cofactor deficiency AR 7 35
MOCS2 Molybdenum cofactor deficiency AR 10 15
MOGS Congenital disorder of glycosylation AR 6 6
MPDU1 Congenital disorder of glycosylation AR 6 7
MPI Congenital disorder of glycosylation AR 17 19
MPV17 Mitochondrial DNA depletion syndrome AR 35 42
MTHFR Homocystinuria due to MTHFR deficiency AR 63 120
MTR Methylmalonic acidemia AR 13 40
MTRR Homocystinuria-megaloblastic anemia, cobalamin E AR 9 30
MUT Methylmalonic acidemia due to methylmalonyl-CoA mutase deficiency AR 114 359
MYH3 Arthrogryposis AD 21 35
MYOT Myopathy, myofibrillar, Muscular dystrophy, limb-girdle, 1A, Myopathy, spheroid body AD 7 16
NAGA Kanzaki disease, Alpha-n-acetylgalactosaminidase deficiency, Schindler disease type I, Schindler disease type III AR 6 9
NAGLU Mucopolysaccharidosis (Sanfilippo syndrome), Charcot-Marie-Tooth disease, axonal, type 2V AR 35 168
NAGS N-acetylglutamate synthase deficiency AR 11 46
NBAS Infantile liver failure syndrome 2, Short stature, optic nerve atrophy, and Pelger-Huet anomaly (SOPH syndrome) AR 23 39
NDUFAF2 Mitochondrial complex I deficiency, Leigh syndrome AR 10 8
NDUFS1 Mitochondrial complex I deficiency AR 22 27
NEU1 Sialidosis AR 22 60
NFU1 Multiple mitochondrial dysfunctions syndrome 1 AR 6 15
NGLY1 Congenital disorder of deglycosylation AR 24 22
NHLRC1 Epilepsy, progressive myoclonic AR 15 70
NIPA2 Hypomagnesemia AD/AR 1 4
NPC1 Niemann-Pick disease AR 120 453
NPC2 Niemann-pick disease AR 16 27
NT5C3A Uridine 5-prime monophosphate hydrolase deficiency, hemolytic anemia due to AR 10 28
OAT Gyrate atrophy of choroid and retina AR 66 70
OPA1 Optic atrophy, Optic atrophy 1, Optic atrophy with or without deafness, Ophthalmoplegia, myopathy, ataxia, and neuropathy, Behr synrome, Mitochondrial DNA depletion syndrome 14 AD/AR 97 387
OPA3 Optic atrophy, 3-methylglutaconic aciduria AD/AR 9 15
OTC Ornithine transcarbamylase deficiency XL 342 505
OXCT1 Succinyl CoA:3-oxoacid CoA transferase deficiency AR 7 32
PAH Hyperphenylalaninemia, non-PKU mild, Phenylketonuria AR 241 934
PC Pyruvate carboxylase deficiency AR 31 40
PCBD1 Hyperphenylalaninemia, BH4-deficient AR 6 11
PCCA Propionic acidemia AR 48 123
PCCB Propionic acidemia AR 41 114
PCK1 Phosphoenolpyruvate carboxykinase 1 deficiency AD/AR 2 3
PDHA1 Leigh syndrome, Pyruvate dehydrogenase E1-alpha deficiency XL 62 191
PDHB Pyruvate dehydrogensae E1-beta deficiency AR 4 13
PDHX Pyruvate dehydrogenase E3-binding protein deficiency AR 14 22
PDSS1 Coenzyme Q10 deficiency AR 5 3
PDSS2 Coenzyme Q10 deficiency AR 8 3
PDX1 Pancreatic agenesis, Neonatal diabetes mellitus, Maturity-onset diabetes of the young, type 4, Lactic acidemia due to PDX1 deficiency AD/AR 10 26
PEPD Prolidase deficiency AR 12 30
PEX1 Heimler syndrome, Peroxisome biogenesis factor disorder 1A, Peroxisome biogenesis factor disorder 1B AR 80 132
PEX2 Zellweger syndrome, Peroxisome biogenesis disorder AR 11 18
PEX3 Zellweger syndrome, Peroxisome biogenesis disorder AR 4 10
PEX5 Adrenoleukodystrophy, neonatal, Rhizomelic chondrodysplasia punctata, Zellweger syndrome, Peroxisome biogenesis disorder AR 8 14
PEX6 Heimler syndrome, Peroxisome biogenesis disorder 4A, Peroxisome biogenesis disorder 4B AR 32 106
PEX7 Refsum disease, Rhizomelic CDP type 1 AR 37 52
PEX10 Adrenoleukodystrophy, neonatal, Zellweger syndrome, Peroxisome biogenesis disorder, Ataxia AR 19 29
PEX11B Zellweger syndrome, Peroxisome biogenesis disorder AR 5 7
PEX12 Zellweger syndrome, Peroxisome biogenesis disorder AR 22 37
PEX13 Adrenoleukodystrophy, neonatal, Zellweger syndrome, Peroxisome biogenesis disorder AR 5 10
PEX14 Peroxisome biogenesis factor disorder 14, Zellweger syndrome AR 5 4
PEX16 Zellweger syndrome, Peroxisome biogenesis disorder AR 8 12
PEX19 Peroxisome biogenesis disorder, 19, Zellweger syndrome AR 3 3
PEX26 Adrenoleukodystrophy, neonatal, Zellweger syndrome, Peroxisome biogenesis disorder AR 13 27
PFKM Glycogen storage disease AR 11 26
PGAM2 Glycogen storage disease AR 3 10
PGK1 Phosphoglycerate kinase 1 deficiency XL 15 26
PGM1 Congenital disorder of glycosylation AR 10 30
PHKA1 Glycogen storage disease XL 7 8
PHKA2 Glycogen storage disease XL 25 113
PHKB Glycogen storage disease AR 7 25
PHKG2 Glycogen storage disease AR 7 31
PHYH Refsum disease AR 11 36
PLIN1 Lipodystrophy, familial partial AD 3 5
PMM2 Congenital disorder of glycosylation AR 62 127
PNP Purine nucleoside phosphorylase deficiency AR 11 33
PNPLA2 Neutral lipid storage disease with myopathy AR 12 36
POLG POLG-related ataxia neuropathy spectrum disorders, Sensory ataxia, dysarthria, and ophthalmoparesis, Alpers syndrome, Progressive external ophthalmoplegia with mitochondrial DNA deletions, Mitochondrial DNA depletion syndrome AD/AR 90 280
POLG2 Progressive external ophthalmoplegia with mitochondrial DNA deletions AD 5 13
PPARG Insulin resistance, Lipodystrophy, familial, partial AD/Digenic (Severe digenic insulin resistance can be due to digenic mutations in PPP1R3A and PPARG) 19 48
PPOX Porphyria variegata AD/AR 16 181
PPT1* Ceroid lipofuscinosis, neuronal AR 86 77
PRKAG2# Hypertrophic cardiomyopathy (HCM), Wolff-Parkinson-White syndrome, Glycogen storage disease of heart, lethal congenital AD 17 56
PRKAG3 Increased glyogen content in skeletal muscle AD 1 1
PRODH* Hyperprolinemia AR 44 10
PRPS1* Deafness, Phosphoribosylpyrophosphate synthetase I superactivity, Arts syndrome, Charcot-Marie-Tooth disease, X-linked recessive, 5, Nonsyndromic sensorineural deafness, 2, X-linked XL 27 31
PSAP Krabbe disease, atypical, Metachromatic leukodystrophy due to saposin-b deficiency, Combined saposin deficiency, Gaucher disease, atypical, due to saposin C deficiency AR 18 26
PTF1A Pancreatic and cerebellar agenesis, Pancreatic agenesis 2 AR 4 15
PTRF Lipodystrophy, congenital generalized AR 9 15
PTS Hyperphenylalaninemia, BH4-deficient AR 19 92
PYGL Glycogen storage disease AR 20 44
PYGM Glycogen storage disease AR 65 165
QDPR Hyperphenylalaninemia, BH4-deficient AR 13 61
RAI1 Smith-Magenis syndrome AD 35 109
RBCK1 Polyglucosan body myopathy AR 10 14
REN Hyperuricemic nephropathy, Hyperproreninemia, familial, Renal tubular dysgenesis AD 8 18
RFT1 Congenital disorder of glycosylation AR 10 10
RNASEH2A Aicardi-Goutières syndrome AR 13 21
RNASEH2B Aicardi-Goutières syndrome AR 13 40
RNASEH2C Aicardi-Goutières syndrome AR 6 14
RRM2B Progressive external ophthalmoplegia with mitochondrial DNA deletions, Mitochondrial DNA depletion syndrome AD/AR 42 41
RYR1 Central core disease, Malignant hyperthermia, Minicore myopathy with external ophthalmoplegia, Centronuclear myopathy, Minicore myopathy, Multicore myopathy AD/AR 202 632
SAMHD1 Aicardi-Goutières syndrome, Chilblain lupus 2 AR 23 55
SARS2 Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis AR 6 5
SCN4A Hyperkalemic periodic paralysis, Myotonia, potassium-aggravated, Paramyotonia congenita, Myasthenic syndrome, congenital, Normokalemic potassium-sensitive periodic paralysis AD/AR 57 112
SEC23B Anemia, dyserythropoietic congenital AR 15 120
SERAC1 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome AR 23 48
SERPINA1 Alpha-1-antitrypsin deficiency AR 46 80
SGSH Mucopolysaccharidosis (Sanfilippo syndrome) AR 35 147
SI Sucrase-isomaltase deficiency, congenital AR 12 23
SLC2A1 Stomatin-deficient cryohydrocytosis with neurologic defects, Epilepsy, idiopathic generalized, GLUT1 deficiency syndrome AD/AR 98 262
SLC2A2 Glycogen storage disease, Fanconi-Bickel syndrome, Neonatal diabetes mellitus AR 22 72
SLC3A1 Cystinuria AR 18 202
SLC5A1 Glucose/galactose malabsorption AR 3 55
SLC6A8* Creatine deficiency syndrome XL 32 128
SLC6A9 Glycine encephalopathy with normal serum glycine AR 5 3
SLC6A19 Hartnup disease AR 8 23
SLC7A7 Lysinuric protein intolerance AR 52 66
SLC7A9 Cystinuria AD/AR 20 135
SLC12A3 Gitelman syndrome AR 44 482
SLC16A1 Hyperinsulinemic hypoglycemia, familial, Erythrocyte lactate transporter defect, Monocarboxylate transporter 1 deficiency, Myoclonic-atonic epilepsy AD/AR 12 14
SLC17A5 Sialuria, Finnish (Salla disease), Infantile sialic acid storage disorder AR 41 52
SLC22A5 Carnitine deficiency, systemic primary AR 84 150
SLC25A1 Combined D-2- and L-2-hydroxyglutaric aciduria AR 8 16
SLC25A3 Micochondrial phosphate carrier deficiency AR 2 5
SLC25A4 Progressive external ophthalmoplegia with mitochondrial DNA deletions, Mitochondrial DNA depletion syndrome AD/AR 12 15
SLC25A13 Citrin deficiency AR 25 109
SLC25A15* Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome AR 22 36
SLC25A20 Carnitine-acylcarnitine translocase deficiency AR 14 42
SLC25A26 Combined oxidative phosphorylation deficiency 28 AR 4 4
SLC30A10 Hypermanganesemia with dystonia, polycythemia, and cirrhosis AR 15 15
SLC35A1 Congenital disorder of glycosylation AR 4 4
SLC35A2 Congenital disorder of glycosylation XL 15 15
SLC35C1 Congenital disorder of glycosylation, Leukocyte adhesion deficiency AR 6 7
SLC37A4 Glycogen storage disease AR 29 109
SLC39A4 Acrodermatitis enteropathica AR 13 50
SLC40A1 Hemochromatosis AD 19 61
SLC46A1 Folate malabsorption AR 17 20
SMPD1 Niemann-Pick disease AR 84 249
SPG7 Spastic paraplegia AR 64 108
SRD5A3* Kahrizi syndrome, Congenital disorder of glycosylation AR 13 16
SSR4 Congenital disorder of glycosylation XL 5 6
STT3A Congenital disorder of glycosylation AR 1 1
STT3B Congenital disorder of glycosylation AR 1 2
SUCLA2 Mitochondrial DNA depletion syndrome AR 9 27
SUCLG1 Mitochondrial DNA depletion syndrome AR 11 28
SUGCT Glutaric aciduria III AR 6 5
SUMF1 Multiple sulfatase deficiency AR 21 52
SUOX Sulfocysteinuria AR 6 28
TANGO2 Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration (MECRCN) AR 13 9
TAT Tyrosinemia, type II AR 7 36
TAZ 3-Methylglutaconic aciduria, (Barth syndrome) XL 42 153
TBC1D4 Diabetes mellitus, noninsulin-dependent AR 1 2
TCF4 Corneal dystrophy, Fuchs endothelial, Pitt-Hopkins syndrome AD 86 141
TCN2 Transcobalamin II deficiency AR 9 33
TFR2 Hemochromatosis AR 18 50
TIMM8A* Mohr-Tranebjaerg syndrome, Jensen syndrome, Opticoacoustic nerve atrophy with dementia XL 10 21
TK2 Mitochondrial DNA depletion syndrome AR 38 45
TMEM70 Mitochondrial complex V (ATP synthase) deficiency AR 11 18
TMEM126A Optic atrophy AR 2 1
TMEM165 Congenital disorder of glycosylation AR 4 6
TPMT* Thiopurine S-methyltransferase deficiency AR 16
TPP1 Spinocerebellar ataxia, Neuronal ceroid lipofuscinosis type 2 AR 56 110
TREX1 Vasculopathy, retinal, with cerebral leukodystrophy, Chilblain lupus, Aicardi-Goutières syndrome AD/AR 30 68
TRIM37 Mulibrey nanism AR 19 21
TRPM6 Hypomagnesemia, intestinal AR 15 59
TUSC3 Mental retardation AR 4 14
TYMP Mitochondrial DNA depletion syndrome AR 85 94
UCP2 Hyperinsulinism AD/AR 7
UMOD Familial juvenile hyperuricemic nephropathy, Glomerulocystic kidney disease with hyperuricemia and isosthenuria, Medullary cystic kidney disease 2 AD 27 100
UMPS Orotic aciduria AR 3 12
UPB1 Beta-ureidopropionase deficiency AR 5 17
UROD Porphyria cutanea tarda, Porphyria, hepatoerythropoietic AD/AR 15 122
UROS Porphyria, congenital erythropoietic AR 22 49
WFS1 Wolfram syndrome, Deafness, Wolfram-like syndrome, autosomal dominant, Deafness, autosomal dominant 6/14/38, Cataract 41 AD/AR 68 351
XDH Xanthinuria, type I AR 7 21
ZMPSTE24 Restrictive dermopathy, lethal, Mandibuloacral dysplasia with B lipodystrophy AD/AR 14 33

* 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
ABCC8 Chr11:17498513 c.-190C>G NM_000352.3
ABCC8 Chr11:17465872 c.1333-1013A>G NM_000352.3
ACADM Chr1:76200457 c.388-19T>A NM_000016.4
ACADM Chr1:76211473 c.600-18G>A NM_000016.4 rs370523609
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
ADA Chr20:43248503 c.1079-15T>A NM_000022.2 rs387906268
ADA Chr20:43249076 c.976-34G>A NM_000022.2
ADSL Chr22:40742514 c.-49T>C NM_000026.2
AGL Chr1:100381954 c.4260-12A>G NM_000028.2 rs369973784
ALAD Chr9:116153914 c.165-11C>A NM_000031.5
ALAD Chr9:116153914 c.165-11C>T NM_000031.5 rs749066913
ALAS2 ChrX:55054634 c.-15-2186C>G NM_000032.4
ALAS2 ChrX:55054635 c.-15-2187T>C NM_000032.4
ALAS2 ChrX:55054636 c.-15-2188A>G NM_000032.4
ALAS2 ChrX:55057617 c.-258C>G NM_000032.4 rs140772352
ALDH7A1 Chr5:125907053 c.696-502G>C NM_001182.4
ALDOB Chr9:104197990 c.-11+1G>C NM_000035.3 rs181639417
ALG6 Chr1:63871975 c.347-13C>G NM_013339.3
AMT Chr3:49459938 c.-55C>T NM_000481.3 rs386833677
ARG1 Chr6:131901748 c.306-611T>C NM_000045.3
ARSA Chr22:51064121 c.1108-12C>G NM_000487.5 rs757806374
ASS1 Chr9:133332669 c.175-1119G>A NM_000050.4
ASS1 Chr9:133355236 c.773+49C>T NM_000050.4 rs763389916
ATP7B Chr13:52585596 c.-123C>A NM_000053.3
ATP7B Chr13:52585606 c.-133A>C NM_000053.3
ATP7B Chr13:52585683 c.-210A>T NM_000053.3
ATP7B Chr13:52585915 c.-442G>A NM_000053.3
ATP7B Chr13:52585551 c.-78A>C NM_000053.3
ATP7B Chr13:52518439 c.3061-12T>A NM_000053.3
BCKDHA Chr19:41930736 c.*223T>A NM_000709.3 rs373164531
BCS1L Chr2:219524871 c.-147A>G NM_004328.4
BSCL2 Chr11:62470032 c.405-11A>G NM_001122955.3
BTD Chr3:15687154 c.*159G>A NM_000060.2 rs530872564
CASR Chr3:121994640 c.1378-19A>C NM_001178065.1
CLCN1 Chr7:143013247 c.-59C>A NM_000083.2
CLN3 Chr16:28497984 c.461-13G>C NM_000086.2 rs386833721
COG5 Chr7:106898843 c.1669-15A>G NM_006348.3
COG6 Chr13:40273614 c.1167-24A>G NM_020751.2 rs730882236
COL2A1 Chr12:48379984 c.1527+135G>A NM_001844.4
CPOX Chr3:98300369 c.1173-14T>G NM_000097.5
CPOX Chr3:98310014 c.557-15C>G NM_000097.5
CPS1 Chr2:211539387 c.4102-239A>G NM_001875.4
CTNS Chr17:3539712 c.-643G>T NM_004937.2
CTNS Chr17:3552117 c.141-24T>C NM_001031681.2
CTNS Chr17:3563518 c.971-12G>A NM_001031681.2 rs375952052
CTSC Chr11:88070895 c.-55C>A NM_001814.4 rs766114323
D2HGDH Chr2:242680425 c.293-23A>G NM_152783.3
DBT Chr1:100661453 c.*358A>C NM_001918.3
DBT Chr1:100672742 c.1018-550A>G NM_001918.3 rs796052135
DGUOK Chr2:74177701 c.444-11C>G NM_080916.2 rs536746349
DGUOK Chr2:74177650 c.444-62C>A NM_080916.2
DHDDS Chr1:26774026 c.441-24A>G NM_024887.3 rs764831063
DYSF Chr2:71840553 c.4410+13T>G NM_003494.3
ETFDH Chr4:159593534 c.-75A>G NM_004453.2
FECH Chr18:55254103 c.-251G>C NM_000140.3
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
GALC Chr14:88459917 c.-74T>A NM_001201402.1
GALK1 Chr17:73761239 c.-22T>C NM_000154.1 rs545362817
GALNS Chr16:88908390 c.245-11C>G NM_000512.4
GALT Chr9:34646606 c.-96T>G NM_000155.3
GALT Chr9:34648519 c.687+66T>A NM_000155.3
GALT Chr9:34648904 c.820+13A>G NM_000155.3 rs111033768
GALT Chr9:34647075 c.83-11T>G NM_000155.3
GAMT Chr19:1399508 c.391+15G>T NM_138924.2 rs367567416
GBE1 Chr3:81542963 c.2053-3358_2053-3350delGTGTGGTGGinsTGTTTTTTACATGACAGGT NM_000158.3
GCDH Chr19:13010271 c.1244-11A>G NM_000159.3
GCK Chr7:44229109 c.-557G>C NM_000162.3
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
GNPTG Chr16:1412562 c.610-16_609+28del NM_032520.4 rs193302853
GYG1 Chr3:148717967 c.481+3276C>G NM_004130.3
HADH Chr4:108945190 c.636+471G>T NM_001184705.2 rs786200932
HADH Chr4:108948955 c.709+39C>G NM_001184705.2
HADHB Chr2:26500642 c.442+614A>G NM_000183.2
HAMP Chr19:35773328 c.-153C>T NM_021175.2 rs142126068
HAMP Chr19:35773456 c.-25G>A NM_021175.2
HAMP Chr19:35773453 c.-28G>T NM_021175.2
HCFC1 ChrX:153237261 c.-970T>C NM_005334.2 rs398122908
HEXB Chr5:74014605 c.1243-17A>G NM_000521.3
HEXB Chr5:74016442 c.1509-26G>A NM_000521.3 rs201580118
HEXB Chr5:74016926 c.1614-16_1615dupTTCATGTTATCTACAGAC NM_000521.3 rs756912360
HFE Chr6:26087649 c.-20G>A NM_000410.3 rs138378000
HMBS Chr11:118955622 c.-122T>A NM_000190.3
HMBS Chr11:118955474 c.-270G>A NM_000190.3
HMBS Chr11:118955413 c.-331C>T NM_000190.3
HMBS Chr11:118956445 c.33+669A>G NM_000190.3
HMBS Chr11:118958944 c.34-21A>G NM_000190.3
HMBS Chr11:118960503 c.344+33G>T NM_000190.3 rs374793428
HMBS Chr11:118960990 c.498+15G>T NM_000190.3 rs372555494
HMBS Chr11:118960997 c.498+22G>A NM_000190.3 rs373035384
HMBS Chr11:118963451 c.772-17A>G NM_000190.3 rs149710332
HMBS Chr11:118959325 c.88-20A>C NM_000190.3
HNF1A Chr12:121416453 c.-119G>A NM_000545.5 rs371945966
HNF1A Chr12:121416448 c.-124G>C NM_000545.5 rs563304627
HNF1A Chr12:121416385 c.-187C>A/T NM_000545.5
HNF1A Chr12:121416354 c.-218T>C NM_000545.5
HNF1A Chr12:121416314 c.-258A>G NM_000545.5 rs756136537
HNF1A Chr12:121416289 c.-283A>C NM_000545.5
HNF1A Chr12:121416285 c.-287G>A NM_000545.5
HNF1A Chr12:121416281 c.-291T>C NM_000545.5 rs534474388
HNF1A Chr12:121416110 c.-462G>A NM_000545.5
HNF1A Chr12:121416034 c.-538G>C NM_000545.5
HNF1A Chr12:121416510 c.-62C>G NM_000545.5 rs753567412
HNF1A Chr12:121416475 c.-97T>G NM_000545.5
HNF4A Chr20:42984309 c.-136A>G NM_175914.4
HNF4A Chr20:42984299 c.-146T>C NM_175914.4
HNF4A Chr20:42984276 c.-169C>T NM_175914.4
HNF4A Chr20:42984271 c.-174T>C NM_175914.4
HNF4A Chr20:42984264 c.-181G>A NM_175914.4
HNF4A Chr20:42984253 c.-192C>G NM_175914.4
HNF4A Chr20:43036000 c.291-21A>G NM_000457.4
HPRT1 ChrX:133594415 c.27+47C>T NM_000194.2
HPRT1 ChrX:133625464 c.402+1229A>G NM_000194.2
HPRT1 ChrX:133628822 c.485+1202T>A NM_000194.2
HPRT1 ChrX:133632625 c.533-13T>G NM_000194.2
IDS ChrX:148564764 c.1181-15C>A NM_000202.5
IDS ChrX:148578704 c.709-657G>A NM_000202.5
ISCU Chr12:108961426 c.418+382G>C NM_213595.2 rs767000507
KCNJ11 Chr11:17409772 c.-134G>T NM_000525.3 rs387906398
KCNJ11 Chr11:17409692 c.-54C>T NM_000525.3
L2HGDH Chr14:50735527 c.906+354G>A NM_024884.2
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
MCEE Chr2:71337896 c.379-644A>G NM_032601.3
MLYCD Chr16:83948547 c.949-14A>G NM_012213.2 rs761146008
MOCS1 Chr6:39874534 c.*365_*366delAG NM_005943.5 rs397518419
MTHFR Chr1:11863212 c.-13-28_-13-27delCT NM_005957.4 rs786204005
MTHFR Chr1:11850973 c.1753-18G>A NM_005957.4 rs777661576
MTR Chr1:237057461 c.3205-196A>G NM_000254.2 rs544410324
MTR Chr1:236971838 c.340-166A>G NM_000254.2
MTR Chr1:236977232 c.609+1088G>A NM_000254.2 rs752526782
MTRR Chr5:7883859 c.984+469T>C NM_024010.2
MUT Chr6:49427219 c.-39-1G>A NM_000255.3
MUT Chr6:49404228 c.1957-892C>A NM_000255.3
MUT Chr6:49404235 c.1957-899A>G NM_000255.3
NAGS Chr17:42078968 c.-3063C>A NM_153006.2
NPC1 Chr18:21132700 c.1554-1009G>A NM_000271.4
NPC1 Chr18:21137182 c.882-28A>G/T NM_000271.4
OPA1 Chr3:193374829 c.2179-40G>C NM_130837.2
OPA1 Chr3:193335986 c.610+360G>A NM_130837.2
OPA1 Chr3:193335990 c.610+364G>A NM_130837.2
OTC ChrX:38272343 c.1005+1091C>G NM_000531.5
OTC ChrX:38260946 c.540+265G>A NM_000531.5
OTC ChrX:38269404 c.867+1126A>G NM_000531.5
PAH Chr12:103232809 c.*144A>G NM_000277.1 rs375319584
PAH Chr12:103237568 c.1066-11G>A NM_000277.1 rs5030855
PAH Chr12:103237570 c.1066-13T>G NM_000277.1
PAH Chr12:103237571 c.1066-14C>G NM_000277.1 rs62507334
PAH Chr12:103237407 c.1199+17G>A NM_000277.1 rs62508613
PAH Chr12:103237404 c.1199+20G>C NM_000277.1 rs62509018
PAH Chr12:103288709 c.169-13T>G NM_000277.1 rs62507341
PAH Chr12:103271835 c.353-507G>T NM_000277.1 rs863225301
PC Chr11:66620883 c.1369-29A>G NM_000920.3
PCCA Chr13:100958030 c.1285-1416A>G NM_000282.3
PCCB Chr3:136003251 c.714+462A>G NM_001178014.1
PDHA1 ChrX:19377861 c.*79_*90dupAGTCAATGAAAT NM_001173454.1
PDHA1 ChrX:19372579 c.625-30G>A NM_001173454.1
PDHA1 ChrX:19373648 c.873+26G>A NM_001173454.1
PDHX Chr11:34988372 c.816+11C>G NM_003477.2
PEX6 Chr6:42933952 c.2300+28G>A NM_000287.3 rs267608237
PEX6 Chr6:42933858 c.2301-15C>G NM_000287.3 rs267608236
PEX7 Chr6:137143759 c.-45C>T NM_000288.3 rs267608252
PFKM Chr12:48535459 c.1626-64A>G NM_001166686.1
PGM1 Chr1:64113966 c.1199-222G>T NM_001172818.1
PGM1 Chr1:64124734 c.1654-523G>A NM_001172818.1
PHKG2 Chr16:30762416 c.96-11G>A NM_000294.2 rs751600886
PMM2 Chr16:8898599 c.179-25A>G NM_000303.2 rs760689221
PMM2 Chr16:8941558 c.640-23A>G NM_000303.2
PNP Chr14:20942914 c.286-18G>A NM_000270.3
PPOX Chr1:161135755 c.-655G>C NM_000309.3
PPOX Chr1:161140686 c.1249-11T>G NM_000309.3 rs780277900
PPT1 Chr1:40539203 c.*526_*529delATCA NM_000310.3 rs386833624
PPT1 Chr1:40558194 c.125-15T>G NM_000310.3 rs386833629
PSAP Chr10:73583679 c.778-26C>A NM_001042465.1
PTF1A Chr10:23508305 c.*25470A>G NM_178161.2
PTF1A Chr10:23508363 c.*25528A>G NM_178161.2
PTF1A Chr10:23508365 c.*25530A>G NM_178161.2
PTF1A Chr10:23508437 c.*25602A>G NM_178161.2
PTF1A Chr10:23508446 c.*25611A>C NM_178161.2
PTS Chr11:112100215 c.164-716A>T NM_000317.2
PTS Chr11:112099026 c.84-291A>G NM_000317.2
PTS Chr11:112098994 c.84-323A>T NM_000317.2 rs794726657
PYGM Chr11:64525847 c.425-26A>G NM_005609.2 rs764313717
PYGM Chr11:64523631 c.661-601G>A NM_005609.2
QDPR Chr4:17500790 c.436+2552A>G NM_000320.2
RNASEH2B Chr13:51501530 c.65-13G>A NM_024570.3
RYR1 Chr19:39074134 c.14647-1449A>G NM_000540.2 rs193922886
RYR1 Chr19:39073707 c.14647-1876C>T NM_000540.2 rs193922885
RYR1 Chr19:38997317 c.8692+131G>A NM_000540.2
SEC23B Chr20:18488615 c.-16A>G NM_006363.4
SEC23B Chr20:18488060 c.-571A>G NM_006363.4 rs559854357
SEC23B Chr20:18526845 c.1743+168A>G NM_006363.4 rs111951711
SEC23B Chr20:18491863 c.221+163A>G NM_006363.4 rs573898514
SEC23B Chr20:18491731 c.221+31A>G NM_006363.4
SEC23B Chr20:18492791 c.222-78C>T NM_006363.4 rs150393520
SERPINA1 Chr14:94854896 c.-5+1G>A NM_000295.4 rs775786225
SLC12A3 Chr16:56914462 c.1567+297T>G NM_000339.2
SLC12A3 Chr16:56917770 c.1670-191C>T NM_000339.2 rs374182921
SLC12A3 Chr16:56927219 c.2548+253C>T NM_000339.2
SLC12A3 Chr16:56903992 c.602-16G>A NM_000339.2 rs750901478
SLC16A1 Chr1:113498814 c.-202G>A NM_003051.3 rs387906403
SLC16A1 Chr1:113499002 c.-391_-390insACGCCGGTCACGTGGCGGGGTGGGG NM_003051.3 rs606231172
SLC22A5 Chr5:131714054 c.394-16T>A NM_003060.3 rs775097754
SLC22A5 Chr5:131722665 c.825-52G>A NM_003060.3
SLC2A1 Chr1:43395462 c.680-11G>A NM_006516.2
SLC2A2 Chr3:170745041 c.-582A>C NM_000340.1
SLC39A4 Chr8:145641963 c.192+19G>A NM_130849.3 rs368996660
SLC3A1 Chr2:44528119 c.1012-23C>G NM_000341.3
STT3B Chr3:31663820 c.1539+20G>T NM_178862.1
TCN2 Chr22:31011112 c.581-176A>G NM_000355.3 rs372866837
TCN2 Chr22:31011112 c.581-176A>T NM_000355.3
TIMM8A ChrX:100601671 c.133-23A>C NM_004085.3 rs869320666
TMEM165 Chr4:56284334 c.792+182G>A NM_018475.4 rs793888506
TPP1 Chr11:6637752 c.887-18A>G NM_000391.3
TRIM37 Chr17:57106096 c.1949-12A>G NM_015294.3
UROS Chr10:127511774 c.-203T>C NM_000375.2 rs869320670
UROS Chr10:127511794 c.-223C>A NM_000375.2 rs869320669
UROS Chr10:127505271 c.-26-177T>A NM_000375.2
UROS Chr10:127505271 c.-26-177T>C NM_000375.2 rs397515348
UROS Chr10:127505277 c.-26-183G>A NM_000375.2 rs397515349
UROS Chr10:127505287 c.-26-193C>A NM_000375.2 rs397515350
UROS Chr10:127505287 c.-26-193C>G NM_000375.2
UROS Chr10:127505291 c.-26-197C>A NM_000375.2 rs397515351
UROS Chr10:127477605 c.661-31T>G NM_000375.2 rs750180293
WFS1 Chr4:6271704 c.-43G>T NM_006005.3

Test strength

All exons of the GBA gene have segmentally duplicated pseudogenes that reduce sensitivity of NGS diagnostics in general. However, Blueprint Genetics custom assay has good coverage (>20x) with high mapping rates (mapping quality >40) for 100.0% of the target regions in GBA gene. Our validation showed high mean coverage of 184X for the GBA gene. Thus, our NGS Panel is not expected to have major limitations in detecting variants in GBA gene although clinical validation has not been performed at large scale for Gaucher disease.

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

All exons of the GBA gene have segmentally duplicated pseudogenes that reduce sensitivity of NGS diagnostics in general. However, Blueprint Genetics custom assay has good coverage (>20x) with high mapping rates (mapping quality >40) for 100.0% of the target regions in GBA gene. Our validation showed high mean coverage of 184X for the GBA gene. Thus, our NGS Panel is not expected to have major limitations in detecting variants in GBA gene although clinical validation has not been performed at large scale for Gaucher disease.

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 metabolism panel covers classical genes associated with Aicardi-Goutières syndrome, inborn error of metabolism, zellweger Syndrome Spectrum, primary CoQ10 deficiency, familial hyperinsulinism, magnesium deficiency, metabolic myopathies, rhabdomyolysis, Mitochondrial DNA depletion syndrome, periodic paralysis and rhizomelic chondrodysplasia punctata. 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%


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 the following criteria are not Sanger confirmed: the variant quality score is above the internal threshold for a true positive call, and visual check-up of the variant at IGV is in-line with the variant call. 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