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Comprehensive Neuromuscular Sequencing Panel

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
Order Kits
TEST METHODS

NGS Sequencing

Test Code Test Copy GenesCPT Code Copy CPT Codes
4937 ACTA1 81479 Add to Order
AGL 81407
AGRN 81479
ALG14 81479
ALG2 81479
ANO5 81406
ATP2A1 81479
B3GALNT2 81479
B4GAT1 81479
BAG3 81479
BICD2 81479
BIN1 81479
CACNA1S 81479
CAPN3 81406
CAV3 81404
CCDC78 81479
CFL2 81479
CHAT 81479
CHKB 81479
CHRNA1 81479
CHRNB1 81479
CHRND 81479
CHRNE 81479
CHRNG 81479
CLCN1 81406
CNTN1 81479
COL12A1 81479
COL13A1 81479
COL6A1 81407
COL6A2 81407
COL6A3 81407
COLQ 81479
CRYAB 81479
DES 81405
DMD 81408
DNAJB6 81479
DNM2 81479
DOK7 81479
DPAGT1 81479
DPM1 81479
DPM2 81479
DPM3 81479
DYSF 81408
ECEL1 81479
EMD 81405
FHL1 81404
FKRP 81404
FKTN 81405
FLNC 81479
GAA 81406
GBE1 81479
GFPT1 81479
GLE1 81479
GMPPB 81479
GNE 81406
HNRNPA1 81479
HNRNPA2B1 81479
HNRNPDL 81479
ISCU 81479
ISPD 81405
ITGA7 81479
KBTBD13 81479
KLHL40 81479
KLHL41 81479
KLHL9 81479
LAMA2 81408
LARGE1 81479
LDB3 81406
LIMS2 81479
LMNA 81406
LMOD3 81479
MATR3 81479
MEGF10 81479
MICU1 81479
MTM1 81406
MUSK 81479
MYH2 81479
MYH3 81479
MYH7 81407
MYO18B 81479
MYOT 81405
NEB 81408
PFKM 81479
PLEC 81479
PNPLA2 81479
POMGNT1 81406
POMGNT2 81479
POMK 81479
POMT1 81406
POMT2 81406
PREPL 81479
PTRF 81479
PYGM 81406
RAPSN 81479
RYR1 81408
SCN4A 81406
SELENON 81479
SGCA 81405
SGCB 81405
SGCD 81405
SGCG 81405
SIL1 81405
SMCHD1 81479
SNAP25 81479
SQSTM1 81479
STAC3 81479
STIM1 81479
SYNE1 81479
SYT2 81479
TCAP 81479
TIA1 81479
TMEM43 81406
TMEM5 81479
TNNI2 81479
TNNT1 81479
TNNT3 81479
TNPO3 81479
TOR1AIP1 81479
TPM2 81479
TPM3 81479
TRAPPC11 81479
TRIM32 81479
TTN 81479
VCP 81479
Full Panel Price* $2490.00
Test Code Test Copy Genes Total Price CPT Codes Copy CPT Codes
4937 Genes x (124) $2490.00 81404(x3), 81405(x10), 81406(x14), 81407(x5), 81408(x5), 81479(x87) Add to Order
Pricing Comment

If you would like to order a subset of these genes contact us to discuss pricing.

Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Sensitivity

The sensitivity of this panel will vary based on the clinical phenotype of the patient and EMG or muscle biopsy results. In an Italian cohort of 504 patients in which 112 similar neuromuscular genes were tested, a definitive molecular diagnosis was made in 43% of patients (Savarese et al. 2016). In another study in which 44 known muscular dystrophy and myopathy genes were analyzed in 55 unrelated Chinese patients with muscle biopsy confirmed MD or congenital myopathy, 36 (65%) were found to have causative pathogenic variants (Dai Y. et al. 2015). In another recent study in which 180 known or candidate myopathy genes were analyzed, a molecular diagnosis was made in 34% of patients (Evilä et al. 2016).

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 ACTA1$690.00 81479 Add to Order
AGL$690.00 81479
AGRN$690.00 81479
ALG2$690.00 81479
ANO5$690.00 81479
B3GALNT2$690.00 81479
B4GAT1$690.00 81479
BAG3$690.00 81479
BIN1$690.00 81479
CACNA1S$690.00 81479
CAPN3$690.00 81479
CAV3$690.00 81479
CCDC78$690.00 81479
CFL2$690.00 81479
CHAT$690.00 81479
CHKB$690.00 81479
CHRNA1$690.00 81479
CHRNB1$690.00 81479
CHRND$690.00 81479
CHRNE$690.00 81479
CHRNG$690.00 81479
CNTN1$690.00 81479
COL12A1$690.00 81479
COL6A1$690.00 81479
COL6A2$690.00 81406
COL6A3$690.00 81406
COLQ$690.00 81479
CRYAB$690.00 81479
DES$690.00 81479
DMD$690.00 81161
DNAJB6$690.00 81479
DNM2$690.00 81479
DOK7$690.00 81479
DPAGT1$690.00 81479
DPM1$690.00 81479
DPM2$690.00 81479
DPM3$690.00 81479
DYSF$690.00 81479
ECEL1$690.00 81479
EMD$690.00 81404
FKRP$690.00 81479
FKTN$690.00 81479
FLNC$690.00 81479
GAA$690.00 81479
GBE1$690.00 81479
GFPT1$690.00 81479
GLE1$690.00 81479
GMPPB$690.00 81479
GNE$690.00 81479
ISPD$690.00 81479
ITGA7$690.00 81479
KBTBD13$690.00 81479
KLHL40$690.00 81479
KLHL41$690.00 81479
LAMA2$690.00 81479
LARGE1$690.00 81479
LDB3$690.00 81479
LIMS2$690.00 81479
LMNA$690.00 81479
MATR3$690.00 81479
MEGF10$690.00 81479
MTM1$690.00 81479
MUSK$690.00 81479
MYH2$690.00 81479
MYH3$690.00 81479
MYH7$690.00 81479
MYOT$690.00 81479
NEB$690.00 81479
PFKM$690.00 81479
PLEC$690.00 81479
PNPLA2$690.00 81479
POMGNT1$690.00 81479
POMGNT2$690.00 81479
POMK$690.00 81479
POMT1$690.00 81479
POMT2$690.00 81479
PYGM$690.00 81479
RAPSN$690.00 81479
RYR1$690.00 81479
SCN4A$690.00 81479
SELENON$690.00 81479
SGCA$690.00 81479
SGCB$690.00 81479
SGCD$690.00 81479
SGCG$690.00 81404
SIL1$690.00 81479
SMCHD1$690.00 81479
SQSTM1$690.00 81479
STAC3$690.00 81479
STIM1$690.00 81479
SYNE1$690.00 81479
TCAP$690.00 81479
TMEM43$690.00 81479
TMEM5$690.00 81479
TNNI2$690.00 81479
TNNT1$690.00 81479
TNNT3$690.00 81479
TNPO3$690.00 81479
TOR1AIP1$690.00 81479
TPM2$690.00 81479
TPM3$690.00 81479
TRAPPC11$690.00 81479
TRIM32$690.00 81479
TTN$690.00 81479
VCP$690.00 81479
Full Panel Price* $1990.00
Test Code Test Copy Genes Total Price CPT Codes Copy CPT Codes
600 Genes x (105) $1990.00 81161, 81404(x2), 81406(x2), 81479(x100) Add to Order
Pricing Comment

# of Genes Ordered

Total Price

1

$690

2

$730

3

$770

4-10

$840

11-30

$1,290

31-100

$1,670

Over 100

Call for quote

Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Sensitivity

Many of the genes in this panel have no or very few large deletions/duplications reported, indicating clinical sensitivity would be low for this panel. However, the DMD, DYSF, GAA, ISPD, LARGE1, and LAMA2 genes have a higher proportion of gross deletions/duplications reported and could be considered for aCGH testing (Human Gene Mutation Database). Approximately two-thirds of the pathogenic variants in Duchenne muscular dystrophy (DMD) patients are deletions of one or more exons in the DMD gene. The occurrence of deletions is slightly higher in Becker muscular dystrophy (BMD) patients. Duplications are found in approximately 10% of DMD patients and 20% of BMD patients (Monaco et al. 1988; Aartsma-Rus et al. 2006).

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Clinical Features

Neuromuscular disorders (NMDs) are a clinically, pathologically, and genetically heterogeneous group of diseases that impair muscle function or the peripheral nervous system and result in muscle weakness. The clinical diagnosis of these patients is based on clinical presentation, electromyography (EMG), muscle biopsy histopathology, biochemical and genetic testing. Although some NMDs are acquired or pharmaceutical-induced, many have a genetic cause. The age-of-onset of clinical symptoms depends on the specific diagnosis and can range from the neonatal period to adulthood.

The muscular dystrophies are typically diseases of the muscle membrane or supporting proteins and are characterized by ongoing muscle degeneration and regeneration. Patients with a muscular dystrophy can present with elevated creatine kinase (CK) levels, cardiomyopathy, joint contractures, respiratory issues, developmental delay, and in severe cases, brain and eye abnormalities. Myopathies are typically caused by defects in the contractile apparatus of the muscle and are typically considered less progressive than the dystrophies. In general, these patients have muscle weakness and loss in tone and can also exhibit joint contractures, respiratory complications, and spinal deformities. Congenital myasthenic syndromes (CMS) are disorders of the neuromuscular junction resulting from abnormalities of presynaptic, synaptic, or post synaptic proteins. CMS are characterized by fatigable weakness affecting limb, ocular, facial, and bulbar muscles. Neonates present with feeding problems, choking, feeble cry, and muscle weakness.

This panel includes genes for limb girdle muscular dystrophies, congenital muscular dystrophies, congenital myopathies, distal myopathies, myotonias, congenital myastenthic syndrome, and distal arthrogryposis. This panel is intended for patients in whom a muscle disease is suspected. We also offer a comprehensive neuropathy panel.

Genetics

Neuromuscular disorders are genetically heterogenous and can be inherited in an autosomal dominant (AD), autosomal recessive (AR), and X-linked (XL) manner.

See individual gene test descriptions for information on clinical features and molecular biology of gene products.

Testing Strategy

For this NGS test, the full coding regions plus ~20 bp of non-coding DNA flanking each exon are sequenced for each of the genes listed below. Sequencing is accomplished by capturing specific regions with an optimized solution-based hybridization method, followed by massively parallel sequencing of the captured DNA fragments. Additional Sanger sequencing is performed for any regions not captured or with insufficient number of sequence reads. All pathogenic, undocumented and questionable variant calls are confirmed by Sanger sequencing.

This test will cover 99% of the coding exons in the indicated genes plus flanking regions.

Of note, this testing includes coverage of the SELENON (NM_20451.2) c.*1107T>C variant in the 3' UTR, FKTN deep intronic variant c.647+2084G>T, RYR1 deep intronic variants c.14647-1876C>T and c.14647-1449A>G.

This panel does not include analysis of TTN exons 85-95 and 153-155, NEB exon 84, and DPM1 exons 1-2. Sanger coverage of these regions is available upon request; however, very few variants have been reported in these exons (Human Gene Mutation Database). Exons 82-105 of the NEB gene are organized in three nearly identical repetitive blocks of 8 exons each making this region difficult to analyze. Since there are six highly homologous alleles, there is some limitation in variant and zygosity calling in this region. If an undocumented or pathogenic variant is detected in this region via NextGen Sequencing, a unique PCR and Sanger sequencing method will be used for confirmation.

Indications for Test

Individuals with general muscle weakness, elevated creatine kinase (CK) levels, muscle biopsy and/or EMG suggestive of myopathic process.

Genes

Official Gene Symbol OMIM ID
ACTA1 102610
AGL 610860
AGRN 103320
ALG14 612866
ALG2 607905
ANO5 608662
ATP2A1 108730
B3GALNT2 610194
B4GAT1 605517
BAG3 603883
BICD2 609797
BIN1 601248
CACNA1S 114208
CAPN3 114240
CAV3 601253
CCDC78 614666
CFL2 601443
CHAT 118490
CHKB 612395
CHRNA1 100690
CHRNB1 100710
CHRND 100720
CHRNE 100725
CHRNG 100730
CLCN1 118425
CNTN1 600016
COL12A1 120320
COL13A1 120350
COL6A1 120220
COL6A2 120240
COL6A3 120250
COLQ 603033
CRYAB 123590
DES 125660
DMD 300377
DNAJB6 611332
DNM2 602378
DOK7 610285
DPAGT1 191350
DPM1 603503
DPM2 603564
DPM3 605951
DYSF 603009
ECEL1 605896
EMD 300384
FHL1 300163
FKRP 606596
FKTN 607440
FLNC 102565
GAA 606800
GBE1 607839
GFPT1 138292
GLE1 603371
GMPPB 615320
GNE 603824
HNRNPA1 164017
HNRNPA2B1 600124
HNRNPDL 607137
ISCU 611911
ISPD 614631
ITGA7 600536
KBTBD13 613727
KLHL40 615340
KLHL41 607701
KLHL9 611201
LAMA2 156225
LARGE1 603590
LDB3 605906
LIMS2 607908
LMNA 150330
LMOD3 616112
MATR3 164015
MEGF10 612453
MICU1 605084
MTM1 300415
MUSK 601296
MYH2 160740
MYH3 160720
MYH7 160760
MYO18B 607295
MYOT 604103
NEB 161650
PFKM 610681
PLEC 601282
PNPLA2 609059
POMGNT1 606822
POMGNT2 614828
POMK 615247
POMT1 607423
POMT2 607439
PREPL 609557
PTRF 603198
PYGM 608455
RAPSN 601592
RYR1 180901
SCN4A 603967
SELENON 606210
SGCA 600119
SGCB 600900
SGCD 601411
SGCG 608896
SIL1 608005
SMCHD1 614982
SNAP25 600322
SQSTM1 601530
STAC3 615521
STIM1 605921
SYNE1 608441
SYT2 600104
TCAP 604488
TIA1 603518
TMEM43 612048
TMEM5 605862
TNNI2 191043
TNNT1 191041
TNNT3 600692
TNPO3 610032
TOR1AIP1 614512
TPM2 190990
TPM3 191030
TRAPPC11 614138
TRIM32 602290
TTN 188840
VCP 601023
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Alpha-B Crystallinopathy AD,AR 608810
Amyotrophic Lateral Sclerosis Type 20 AD 615426
Arthrogryposis Multiplex Congenita Distal Type 1 AD 108120
Arthrogryposis, Distal, Type 2B AD 601680
Arthrogryposis, distal, type 5D AR 615065
Autosomal Dominant Limb-Girdle Muscular Dystrophy, Type 1E AD 603511
Autosomal Recessive Centronuclear Myopathy AR 255200
Becker Muscular Dystrophy XL 300376
Benign Scapuloperoneal Muscular Dystrophy With Cardiomyopathy AD 181350
Bethlem Myopathy AD,AR 158810
Bethlem Myopathy 2 AR 616471
Brody Myopathy AR 601003
Central Core Disease AR 117000
Congenital Disorder Of Glycosylation Type 1E AR 608799
Congenital Disorder Of Glycosylation Type 1I AR 607906
Congenital Disorder Of Glycosylation Type 1O AR 612937
Congenital Disorder of Glycosylation, Type Iu AR 615042
Congenital Fiber Type Disproportion AD,AR 255310
Congenital Muscular Dystrophy-Dystroglycanopathy (With Brain And Eye Anomalies) Type A5 XL 613153
Congenital Myasthenic Syndrome, Acetazolamide-Responsive AD 614198
Distal Myopathy Markesbery-Griggs Type AR 600334
Duchenne Muscular Dystrophy XL 310200
Emery-Dreifuss Muscular Dystrophy 1, X-Linked XL 310300
Emery-Dreifuss Muscular Dystrophy 4, Autosomal Dominant AD 612998
Emery-Dreifuss Muscular Dystrophy 7, AD AD 614302
Emery-Dreifuss muscular dystrophy-6 AR 300696
Endplate Acetylcholinesterase Deficiency AD,AR 603034
Facioscapulohumeral Muscular Dystrophy 2 AR 158901
Familial Infantile Myasthenia AR 254210
Familial Limb-Girdle Myasthenic Syndrome With Tubular Aggregates AR 610542
Fetal Akinesia Deformation Sequence AR 208150
Freeman-Sheldon Syndrome AD 193700
Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis 3 AD 616437
Fukuyama Congenital Muscular Dystrophy AR 253800
Glycogen Storage Disease Type II AD 232300
Glycogen Storage Disease Type III AR 232400
Glycogen Storage Disease Type IV AR 232500
Glycogen Storage Disease Type V AR 232600
Glycogen Storage Disease Type VII AR 232800
Hyperkalemic Periodic Paralysis; HYPP AD,AR 170500
Hypotonia-Cystinuria Syndrome AR 606407
Inclusion Body Myopathy 3 AD 605637
Inclusion Body Myopathy With Early-Onset Paget Disease And Frontotemporal Dementia AR 167320
Inclusion Body Myopathy with Early-Onset Paget Disease with or without Frontotemporal Dementia 2 AD 615422
Inclusion Body Myopathy with Early-Onset Paget Disease without Frontotemporal Dementia 3 AD 615424
Klippel-Feil Syndrome 4, Autosomal Recessive, with Myopathy and Facial Dysmorphism AR 616549
Lethal Congenital Contracture Syndrome 1 AR 253310
Lethal Congenital Contracture Syndrome 5 AR 615368
Lethal Multiple Pterygium Syndrome AR 253290
Limb-Girdle Muscular Dystrophy, Type 1A AR 159000
Limb-Girdle Muscular Dystrophy, Type 1B AD 159001
Limb-Girdle Muscular Dystrophy, Type 1F AD,AR 608423
Limb-Girdle Muscular Dystrophy, Type 2A AR 253600
Limb-Girdle Muscular Dystrophy, Type 2B AR 253601
Limb-Girdle Muscular Dystrophy, Type 2D AD 608099
Limb-Girdle Muscular Dystrophy, Type 2E AR 604286
Limb-Girdle Muscular Dystrophy, Type 2F AD,AR 601287
Limb-Girdle Muscular Dystrophy, Type 2G AD 601954
Limb-Girdle Muscular Dystrophy, Type 2H AD,AR 254110
Limb-Girdle Muscular Dystrophy, Type 2Y AR 617072
Lipodystrophy, Congenital Generalized, Type 4 AR 613327
Malignant Hyperthermia AD,AR 145600
Malignant Hyperthermia Susceptibility Type 5 AD 601887
Marinesco-Sjogren Syndrome AR 248800
Merosin Deficient Congenital Muscular Dystrophy AR 607855
Minicore Myopathy With External Ophthalmoplegia AR 255320
Miyoshi Muscular Dystrophy 3 AR 613319
Miyoshi Myopathy AR 254130
Muscle Eye Brain Disease AR 253280
Muscular Dystrophy, Congenital, Due To Integrin Alpha-7 Deficiency AR 613204
Muscular Dystrophy, Congenital, LMNA-Related AD 613205
Muscular Dystrophy, Congenital, Megaconial Type AR 602541
Muscular Dystrophy, Limb Girdle, Type 2C AR 253700
Muscular Dystrophy, Limb-Girdle, Type 1C AD,AR 607801
Muscular Dystrophy, Limb-Girdle, Type 1G AD 609115
Muscular Dystrophy, Limb-Girdle, Type 2J AR 608807
Muscular Dystrophy, Limb-Girdle, Type 2L AR 611307
Muscular Dystrophy, Limb-Girdle, Type 2Q AR 613723
Muscular dystrophy, limb-girdle, type 2S AD,AR 615356
Muscular Dystrophy, Limb-Girdle, Type 2W AR 616827
Muscular Dystrophy-Dystroglycanopathy (Congenital with Brain and Eye Anomalies), Type A, 10; MDDGA10 AD 615041
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 AR 615249
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 13 AR 615287
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 AR 615350
Muscular Dystrophy-Dystroglycanopathy (Congenital With Brain And Eye Anomalies), Type A, 2 AR 613150
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 AR 614643
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 11 AR 615181
Muscular Dystrophy-Dystroglycanopathy (Congenital With Mental Retardation), Type B, 6 AR 608840
Muscular Dystrophy-Dystroglycanopathy (Limb-Girdle), Type C, 1 AR 609308
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 AR 615352
Muscular Dystrophy-Dystroglycanopathy (Limb-Girdle), Type C, 2 AR 613158
Muscular Dystrophy-Dystroglycanopathy (Limb-Girdle), Type C, 3 AR 613157
Muscular Dystrophy-Dystroglycanopathy (Limb-Girdle), Type C, 4 AR 611588
Muscular Dystrophy-Dystroglycanopathy (Limb-Girdle), Type C, 5 AR 607155
Myasthenia, Limb-Girdle, Familial AR 254300
Myasthenic Syndrome, Congenital, 15, without Tubular Aggregates AR 616227
Myasthenic Syndrome, Congenital, 18 AD 616330
Myasthenic Syndrome, Congenital, 19 AR 616720
Myasthenic Syndrome, Congenital, 2A, Slow-Channel AD 616313
Myasthenic Syndrome, Congenital, 7, Presynaptic AD 616040
Myasthenic Syndrome, Congenital, 8, with Pre- and Postsynaptic Defects AR 615120
Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency AR 616325
Myasthenic Syndrome, Congenital, Associated With Acetylcholine Receptor Deficiency AR 608931
Myasthenic Syndrome, Congenital, Fast-Channel AD,AR 608930
Myasthenic Syndrome, Congenital, Slow-Channel AD 601462
Myasthenic syndrome, congenital, with tubular aggregates 2 AR 614750
Myofibrillar Myopathy, BAG3-Related AD 612954
Myofibrillar Myopathy, Desmin-Related AD,AR 601419
Myofibrillar Myopathy, Filamin C-Related AD 609524
Myofibrillar Myopathy, ZASP-Related AD 609452
Myopathy with Extrapyramidal Signs AR 615673
Myopathy With Lactic Acidosis, Hereditary AR 255125
Myopathy, Centronuclear AD 614807
Myopathy, Centronuclear, 1 AD 160150
Myopathy, Congenital, Compton-North AR 612540
Myopathy, Distal, 2 AD 606070
Myopathy, Distal, 4 AR 614065
Myopathy, Distal, With Anterior Tibial Onset AR 606768
Myopathy, Early-Onset, Areflexia, Respiratory Distress, And Dysphagia AR 614399
Myopathy, Myofibrillar, Fatal Infantile Hypertonic, Alpha-B Crystallin-Related AD,AR 613869
Myopathy, Myosin Storage AD,AR 608358
Myopathy, Myosin Storage, Autosomal Recessive AR 255160
Myopathy, Reducing Body, X-Linked, Early-Onset, Severe XL 300717
Myopathy, tubular aggregate AR 160565
Myotilinopathy AD 609200
Myotonia Congenita Autosomal Recessive AR 255700
Native American myopathy AR 255995
Nemaline Myopathy 1 AD,AR 609284
Nemaline Myopathy 10 AR 616165
Nemaline Myopathy 2 AR 256030
Nemaline Myopathy 3 AD,AR 161800
Nemaline Myopathy 4 AD 609285
Nemaline Myopathy 5 AR 605355
Nemaline Myopathy 6 AR 609273
Nemaline Myopathy 7 AR 610687
Nemaline Myopathy 8 AR 615348
Nemaline Myopathy 9 AR 615731
Neutral Lipid Storage Disease With Myopathy AR 610717
Nonaka Myopathy AR 605820
Potassium Aggravated Myotonia AD 608390
Rigid Spine Muscular Dystrophy 1 AR 602771
Rippling Muscle Disease AD 606072
Scapuloperoneal Myopathy, Myh7-Related AD 181430
Scapuloperoneal Myopathy, X-Linked Dominant XL 300695
Severe X-Linked Myotubular Myopathy XL 310400
Spinal Muscular Atrophy, Lower Extremity-Predominant, 2 AD 615290
Ullrich Congenital Muscular Dystrophy AR 254090
Walker-Warburg Congenital Muscular Dystrophy AR 236670
Welander distal myopathy AR 604454

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Congenital Disorders of Glycosylation (CDG) Sanger Sequencing Panel 2
Congenital Disorders of Glycosylation, Type Ie (CDG Ie) via the DPM1 Gene
Congenital Disorders of Glycosylation, Type Ii (CDG Ii) via the ALG2 Gene
Congenital Disorders of Glycosylation, Type Io Plus Secondary Dystroglycanopathy via the DPM3 Gene
Congenital Fiber Type Disproportion Sequencing Panel
Congenital Fibrosis of Extraocular Muscles (Ocular Motility Disorder) or Strabismus Syndromes Sequencing Panel with CNV Detection
Congenital Muscular Dystrophy Sequencing Panel
Congenital Muscular Dystrophy, Megaconial Type via the CHKB Gene
Congenital Myasthenic Syndrome Sequencing Panel
Congenital Myasthenic Syndrome via the CHRNE Gene
Congenital Myasthenic Syndrome via the COLQ Gene
Congenital Myasthenic Syndrome via the GFPT1 Gene
Congenital Myasthenic Syndrome via the MUSK Gene
Congenital Myasthenic Syndrome via the SYT2 Gene
Congenital Myasthenic Syndrome With Episodic Apnea via the CHAT Gene
Congenital Myasthenic Syndromes and Lethal Multiple Pterygium Syndrome via the CHRNA1 Gene
Congenital Myasthenic Syndromes and Multiple Pterygium Syndrome via the CHRND Gene
Congenital Myasthenic Syndromes via the CHRNB1 Gene
Congenital Myopathy (Native American Myopathy) via the STAC3 Gene
Core Myopathy Sequencing Panel
Dementia Sequencing Panel
Dilated Cardiomyopathy and Limb-Girdle Muscular Dystrophy Type 2F via the SGCD Gene
Distal Arthrogryposis 2B (Sheldon-Hall Syndrome) via the TNNI2 Gene
Distal Arthrogryposis 2B (Sheldon-Hall Syndrome) via the TNNT3 Gene
Distal Arthrogryposis Sequencing Panel
Distal Arthrogryposis, Autosomal Recessive, Type 5D (DA5D) via the ECEL1 Gene
Distal Hereditary Myopathy Sequencing Panel
Distal Myopathy 2 via the MATR3 Gene
Dynamin-2 Related Disorders via the DNM2 Gene
Dystroglycan-Related Congenital Muscular Dystrophy Sequencing Panel
Dystroglycanopathies via the POMK Gene
Dystroglycanopathy via the B3GALNT2 Gene
Dystroglycanopathy via the FKTN Gene
Dystroglycanopathy via the LARGE1/LARGE Gene
Dystroglycanopathy via the GMPPB Gene
Dystrophinopathy via the DMD Gene
Dystrophinopathy via the DMD Gene
Early-Onset Myopathy, Areflexia, Respiratory Distress, and Dysphagia (EMARDD) via the MEGF10 Gene
Emery-Dreifuss Muscular Dystrophy (EDMD1) via the EMD Gene
Epidermolysis Bullosa and Related Disorders Sequencing Panel with CNV Detection
Epidermolysis Bullosa with Pyloric Atresia via the PLEC Gene
Facioscapulohumeral Muscular Dystrophy 2 via the SMCHD1 Gene
Familial Limb Girdle Myasthenia Syndrome via the DOK7 Gene
Familial Limb Girdle Myasthenic Syndrome via the AGRN Gene
Familial Limb Girdle Myasthenic Syndrome With Tubular Aggregates via the DPAGT1 Gene
Fetal Akinesia Deformation Sequence/Lethal Multiple Pterygium Syndrome Sequencing Panel
Fetal Concerns Sequencing Panel with CNV Detection
Glycogen Storage Disease and Disorders of Glucose Metabolism Sequencing Panel
Glycogen Storage Disease Type II (Pompe Disease) via the GAA Gene
Glycogen Storage Disease Type II (Pompe Disease) via the GAA Gene, Exon 18 Deletion
Glycogen Storage Disease Type III via the AGL Gene
Glycogen Storage Disease Type IV via the GBE1 Gene
Glycogen Storage Disease Type VII (Tarui Disease) via the PFKM Gene
Glycogen Storage Disease, Type V (McArdle Disease) via the PYGM Gene - Sequential Test
Glycogen Storage Disease, Type V (McArdle Disease) via the PYGM Gene - Tier 1
Glycogen Storage Disease, Type V (McArdle Disease) via the PYGM Gene - Tier 2
Gnathodiaphyseal Dysplasia via the ANO5 Gene
Hereditary Spastic Paraplegia Comprehensive Sequencing Panel with CNV Detection
Hutchinson-Gilford Progeria Syndrome (HGPS) via the LMNA Gene
Hypertrophic Cardiomyopathy and other MYH7-Related Disorders via the MYH7 Gene
Inclusion Body Myopathy and Autosomal Recessive, Early Onset Myopathy via the MYH2 Gene
Inclusion Body Myopathy-2 (Autosomal Recessive) and Nonaka Myopathy via the GNE Gene
Integrin Alpha 7-Related Congenital Myopathy via the ITGA7 Gene
Laminopathies via the LMNA Gene
Left Ventricular Noncompaction (LVNC) Sequencing Panel with CNV Detection
Limb Girdle Muscular Dystrophy Type 1F via the TNPO3 Gene
Limb Girdle Muscular Dystrophy Type 2A via the CAPN3 Gene
Limb Girdle Muscular Dystrophy Type 2B and Miyoshi Myopathy via the DYSF Gene
Limb Girdle Muscular Dystrophy Type 2I via the FKRP Gene
Limb Girdle Muscular Dystrophy Type 2S (LGMD2S) via the TRAPPC11 Gene
Limb Girdle Muscular Dystrophy Type 2W (LGMD2W) via The LIMS2 Gene
Limb Girdle Muscular Dystrophy, Type 2C (LGMD2C) via the SGCG Gene
Limb Girdle Muscular Dystrophy, Type 2D (LGMD2D) via the SGCA Gene
Limb Girdle Muscular Dystrophy, Type 2E (LGMD2E) via the SGCB Gene
Limb Girdle Muscular Dystrophy, Type 2J and Tibial Muscular Dystrophy via the TTN Gene (exons 307 - 312)
Limb Girdle Muscular Dystrophy, Type 2L (LGMD2L) and Distal Miyoshi Myopathy (MMD3) via the ANO5 Gene
Limb-Girdle Muscular Dystrophy (LGMD) Sequencing Panel
Long QT Syndrome Sequencing Panel
Malignant Hyperthermia Susceptibility Sequencing Panel
Marinesco-Sjogren Syndrome via the SIL1 Gene
Merosin-Deficient Congenital Muscular Dystrophy (MDC1A) via the LAMA2 Gene (Mexican Exon 55 Mutation)
Merosin-Deficient Congenital Muscular Dystrophy (MDC1A) via the LAMA2 Gene
Metabolic Hypoglycemia Sequencing Panel
Metabolic Myopathies, Rhabdomyolysis and Exercise Intolerance Sequencing Panel
Multiple Pterygium Syndrome via the CHRNG Gene
Myofibrillar Myopathy Sequencing Panel
Myofibrillar Myopathy via the CRYAB Gene
Myofibrillar Myopathy via the DES Gene
Myofibrillar Myopathy via the FLNC Gene
Myofibrillar Myopathy via the LDB3 (ZASP) Gene
Myofibrillar Myopathy, Childhood Onset via the BAG3 Gene
Myopathy, Congenital via the TPM3 Gene
Myotilinopathy via the MYOT Gene
Myotonia Congenita via the CLCN1 Gene
Nemaline Myopathy (NEM2) via the Nebulin (NEB) Gene
Nemaline Myopathy 10 via the LMOD3 Gene
Nemaline Myopathy 5 (Amish Nemaline Myopathy) via the TNNT1 Gene
Nemaline Myopathy 7 via the CFL2 Gene
Nemaline Myopathy 9 via the KLHL41 Gene
Nemaline Myopathy Sequencing Panel
Nemaline Myopathy via the KLHL40 Gene
Nemaline Myopathy via the NEB Exon 55 Deletion
Nemaline Myopathy With Cores (NEM6) via the KBTBD13 Gene
Nemaline Myopathy NEB Triplicate Repeat Region, Exons 82-105
Neutral Lipid Storage Disease with Myopathy via the PNPLA2 Gene
Paget Disease of Bone (PDB) Sanger Sequencing Panel
Paget Disease of Bone via the SQSTM1 Gene
Plectinopathy via the PLEC Gene
Primary Periodic Paralysis Sequencing Panel
Pure Hereditary Spastic Paraplegia Sequencing Panel with CNV Detection
Rapsyn-Related Disorders via the RAPSN Gene
Selenoprotein N, 1 via the SELENON/SEPN1 Gene
Sialuria via the GNE Gene, Exon 5
Spinocerebellar Ataxia, Autosomal Recessive-8 (French Canadian Mutation Sanger Sequencing Panel)
Spinocerebellar Ataxia, Autosomal Recessive-8 via the SYNE1 Gene Exons 2-146
Telethoninopathy via the TCAP Gene
Tropomyosin 2-Related Disorders via the TPM2 Gene
Tubular Aggregate Myopathy via the STIM1 Gene
Type IV Voltage-Gated Sodium Channel (Alpha Subunit)-Related Disorders via the SCN4A Gene
Type VI Collagenopathy via the COL6A1 Gene
Type VI Collagenopathy via the COL6A2 Gene
Type VI Collagenopathy via the COL6A3 Gene
Type VI-Related Collagenopathy Sequencing Panel
Type VI-Related Collagenopathy via the COL12A1 Gene
Valosin-Containing Protein-Related Disorders via the VCP Gene
Walker-Warburg Syndrome via the B3GNT1(B4GAT1) Gene
Walker-Warburg Syndrome via the POMGNT1 Gene
Walker-Warburg Syndrome via the POMT1 Gene
Walker-Warburg Syndrome via the POMT2 Gene
Walker-Warburg Syndrome via the TMEM5 Gene
Walker-Warburg Syndrome via the Glycosyltransferase-Like Domain-Containing Protein 2 (POMGNT2) Gene
Walker-Warburg Syndrome via the Isoprenoid Synthase Domain Containing (ISPD) Gene
Welander Distal Myopathy via the TIA1 Gene

CONTACTS

Genetic Counselors
Geneticist
Citations
  • Aartsma-Rus A. et al. 2006. Muscle & Nerve. 34: 135-44. PubMed ID: 16770791
  • Dai Y. et al. 2015. Neuromuscular Disorders. 25: 617-24. PubMed ID: 25987458
  • Evilä A. et al. 2016. Neuromuscular Disorders. 26: 7-15. PubMed ID: 26627873
  • Human Gene Mutation Database (Bio-base).
  • Monaco A.P. et al. 1988. Genomics. 2: 90-5. PubMed ID: 3384440
  • Savarese M. et al. 2016. Neurology. 87: 71-6. PubMed ID: 27281536
Order Kits
TEST METHODS

NextGen Sequencing using PG-Select Capture Probes

Test Procedure

We use a combination of Next Generation Sequencing (NGS) and Sanger sequencing technologies to cover the full coding regions of the listed genes plus ~20 bases of non-coding DNA flanking each exon.  As required, genomic DNA is extracted from the patient specimen.  For NGS, patient DNA corresponding to these regions is captured using an optimized set of DNA hybridization probes.  Captured DNA is sequenced using Illumina’s Reversible Dye Terminator (RDT) platform (Illumina, San Diego, CA, USA).  Regions with insufficient coverage by NGS are covered by Sanger sequencing.  All pathogenic, likely pathogenic, or variants of uncertain significance are confirmed by Sanger sequencing.

For Sanger sequencing, Polymerase Chain Reaction (PCR) is used to amplify targeted regions.  After purification of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  PCR products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In nearly all cases, cycle sequencing is performed separately in both the forward and reverse directions.

Patient DNA sequence is aligned to the genomic reference sequence for the indicated gene region(s). All differences from the reference sequences (sequence variants) are assigned to one of five interpretation categories, listed below, per ACMG Guidelines (Richards et al. 2015).

(1) Pathogenic Variants
(2) Likely Pathogenic Variants
(3) Variants of Uncertain Significance
(4) Likely Benign Variants
(5) Benign, Common Variants

Human Genome Variation Society (HGVS) recommendations are used to describe sequence variants (http://www.hgvs.org).  Rare variants and undocumented variants are nearly always classified as likely benign if there is no indication that they alter protein sequence or disrupt splicing.

Analytical Validity

As of March 2016, 6.36 Mb of sequence (83 genes, 1557 exons) generated in our lab was compared between Sanger and NextGen methodologies. We detected no differences between the two methods. The comparison involved 6400 total sequence variants (differences from the reference sequences). Of these, 6144 were nucleotide substitutions and 256 were insertions or deletions. About 65% of the variants were heterozygous and 35% homozygous. The insertions and deletions ranged in length from 1 to over 100 nucleotides.

In silico validation of insertions and deletions in 20 replicates of 5 genes was also performed. The validation included insertions and deletions of lengths between 1 and 100 nucleotides. Insertions tested in silico: 2200 between 1 and 5 nucleotides, 625 between 6 and 10 nucleotides, 29 between 11 and 20 nucleotides, 25 between 21 and 49 nucleotides, and 23 at or greater than 50 nucleotides, with the largest at 98 nucleotides. All insertions were detected. Deletions tested in silico: 1813 between 1 and 5 nucleotides, 97 between 6 and 10 nucleotides, 32 between 11 and 20 nucleotides, 20 between 21 and 49 nucleotides, and 39 at or greater than 50 nucleotides, with the largest at 96 nucleotides. All deletions less than 50 nucleotides in length were detected, 13 greater than 50 nucleotides in length were missed. Our standard NextGen sequence variant calling algorithms are generally not capable of detecting insertions (duplications) or heterozygous deletions greater than 100 nucleotides. Large homozygous deletions appear to be detectable.   

Analytical Limitations

Interpretation of the test results is limited by the information that is currently available.  Better interpretation should be possible in the future as more data and knowledge about human genetics and this specific disorder are accumulated.

When Sanger sequencing does not reveal any difference from the reference sequence, or when a sequence variant is homozygous, we cannot be certain that we were able to detect both patient alleles.  Occasionally, a patient may carry an allele which does not amplify, due to a large deletion or insertion.   In these cases, the report will contain no information about the second allele.  Our Sanger and NGS Sequencing tests are generally not capable of detecting Copy Number Variants (CNVs).

We sequence all coding exons for each given transcript, plus ~20 bp of flanking non-coding DNA for each exon.  Test reports contain no information about other portions of the gene, such as regulatory domains, deep intronic regions or any currently uncharacterized alternative exons.

In most cases, we are unable to determine the phase of sequence variants.  In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants due to somatic mosaicism is limited.  Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR.

Unless otherwise indicated, DNA sequence data is obtained from a specific cell-type (usually leukocytes from whole blood).   Test reports contain no information about the DNA sequence in other cell-types.

We cannot be certain that the reference sequences are correct.

Rare, low probability interpretations of sequencing results, such as for example the occurrence of de novo mutations in recessive disorders, are generally not included in the reports.

We have confidence in our ability to track a specimen once it has been received by PreventionGenetics.  However, we take no responsibility for any specimen labeling errors that occur before the sample arrives at PreventionGenetics.

Deletion/Duplication Testing Via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

Order Kits

Ordering Options


myPrevent - Online Ordering
  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
REQUISITION FORM
  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

SPECIMEN TYPES
WHOLE BLOOD

(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.

DNA

(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.

CELL CULTURE

(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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