Charcot-Marie-Tooth Neuropathy Panel

  • Is a 105 gene panel that includes assessment of non-coding variants.
  • Is ideal for patients with a clinical suspicion of Charcot-Marie-Tooth neuropathy.

Analysis methods
  • PLUS

4 weeks

Number of genes


Test code


Panel size


CPT code *
* The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.


The Blueprint Genetics Charcot-Marie-Tooth Neuropathy Panel (test code NE1301):

ICD codes

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

Sample Requirements

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

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

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

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

Read more about our sample requirements here.

Charcot-Marie-Tooth (CMT) neuropathy, also known as hereditary motor/sensory neuropathy (HMSN) is the most common genetic cause of neuropathy. Prevalence is estimated to be 1:3,300. CMT is characterized by broad genetic heterogeneity and can be inherited in an autosomal dominant, autosomal recessive or X-linked manner. CMT neuropathy results from involvement of peripheral nerves that can affect the motor system and/or the sensory system. Individuals with CMT experience symmetric, slowly progressive distal motor neuropathy of the arms and legs usually beginning in the first to third decade of life, and resulting in weakness and atrophy of the muscles in the feet and/or hands. Pes cavus foot deformity is common. CMT neuropathies can be divided to demyelinating and axonal forms.

Genes in the Charcot-Marie-Tooth Neuropathy Panel and their clinical significance

Gene Associated phenotypes Inheritance ClinVar HGMD
AARS Epileptic encephalopathy, early infantile, Charcot-Marie-Tooth disease AD/AR 9 16
AGTPBP1 Neuropathy AR 3 1
AIFM1 Deafness, Combined oxidative phosphorylation deficiency 6, Cowchock syndrome XL 27 31
AMACR Alpha-methylacyl-CoA racemase deficiency, Bile acid synthesis defect AR 3 8
ARHGEF10 Slowed nerve conduction velocity AD 4 12
ATAD3A* Harel-Yoon syndrome AD/AR 4 17
ATL1 Spastic paraplegia, Neuropathy, hereditary sensory AD 29 84
ATL3 Neuropathy, hereditary sensory AD 1 4
ATP1A1 Charcot-Marie-Tooth disease AD 8 10
ATP7A Menkes disease, Occipital horn syndrome, Spinal muscular atrophy, distal, X-linked 3 XL 116 354
BAG3 Dilated cardiomyopathy (DCM), Myopathy, myofibrillar AD 39 62
BICD2 Childhood-onset proximal spinal muscular atrophy with contractures AD 12 28
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 AD/AR 34 50
C12ORF65 Spastic paraplegia, Combined oxidative phosphorylation deficiency AR 10 11
CCT5 Neuropathy, hereditary sensory, with spastic paraplegia AR 1 1
CHCHD10 Myopathy, isolated mitochondrial, Frontotemporal dementia and/or amyotrophic lateral sclerosis 2, Spinal muscular atrophy, Jokela type AD 4 26
COA7 Spinocerebellar ataxia, Charcot-Marie-Tooth disease AR 2 7
COX10* Leigh syndrome, Mitochondrial complex IV deficiency AR 52 13
COX6A1 Charcot-Marie-Tooth disease AR 2 1
CTDP1 Congenital cataracts, facial dysmorphism, and neuropathy AR 1 1
DCAF8 Giant axonal neuropathy 2, autosomal dominant AD 1 1
DCTN1 Perry syndrome, Neuropathy, distal hereditary motor AD 10 52
DHTKD1 2-aminoadipic and 2-oxoadipic aciduria, Charcot-Marie-Tooth disease AD/AR 11 18
DNM2 Myopathy, Lethal akinesia and musculoskeletal abnormalities, with brain and retinal hemorrhages, Charcot-Marie-Tooth disease AD/AR 28 47
DNMT1 Neuropathy, hereditary sensory, Cerebellar ataxia, deafness, and narcolepsy AD 9 20
DST Neuropathy, hereditary sensory and autonomic AR 13 7
DYNC1H1 Spinal muscular atrophy, Charcot-Marie-Tooth disease, Mental retardation AD 60 71
EGR2 Neuropathy, Dejerine-Sottas disease, Charcot-Marie-Tooth disease AD/AR 13 21
FAM134B Neuropathy, hereditary sensory and autonomic AR 8 5
FBLN5 Cutis laxa, Macular degeneration, age-related AD/AR 13 22
FGD4 Charcot-Marie-Tooth disease AR 21 27
FIG4 Amyotrophic lateral sclerosis, Polymicrogyria, bilateral occipital, Yunis-Varon syndrome, Charcot-Marie-Tooth disease AD/AR 34 69
FXN* Friedreich ataxia AR 13 63
GAN Giant axonal neuropathy AR 18 76
GARS Neuropathy, distal hereditary motor, Charcot-Marie-Tooth disease AD 19 38
GDAP1 Charcot-Marie-Tooth disease AD/AR 39 100
GJB1 Charcot-Marie-Tooth neuropathy XL 98 495
GNB4 Charcot-Marie-Tooth disease AD 2 5
GNE Proximal myopathy and ophthalmoplegia, Nonaka myopathy, Sialuria AD/AR 78 214
HADHB Trifunctional protein deficiency AR 20 65
HARS Charcot-Marie-Tooth disease, axonal, type 2W, Usher syndrome, type 3B AR 6 12
HINT1 Axonal neuropathy with neuromyotonia AR 11 15
HK1# Hemolytic anemia, nonspherocytic, due to hexokinase deficiency, Retinitis pigmentosa 79, Neuropathy, motor and sensory, Russe type (Charcot-Marie-Tooth disease type 4G) AD/AR 9 7
HSPB1 Neuropathy, distal hereditary motor, Charcot-Marie-Tooth disease AD 27 44
HSPB8 Charcot-Marie-Tooth disease, Distal hereditary motor neuronopathy AD 6 9
IGHMBP2 Spinal muscular atrophy, distal, Charcot-Marie-Tooth disease AR 52 128
IKBKAP Dysautonomia, familial, Hereditary sensory and autonomic neuropathy AR 47 6
INF2 Glomerulosclerosis, Charcot-Marie-Tooth disease AD 20 67
KARS Charcot-Marie-Tooth disease AR 9 23
KIF1A Spastic paraplegia, Neuropathy, hereditary sensory, Mental retardation AD/AR 63 42
KIF1B Pheochromocytoma, Neuroblastoma, Charcot-Marie-Tooth disease, type 2A1 AD 7 12
KIF5A Spastic paraplegia AD 18 62
LDB3 Dilated cardiomyopathy (DCM), Myopathy, myofibrillar AD 9 14
LITAF Charcot-Marie-Tooth disease AD 10 18
LMNA Heart-hand syndrome, Slovenian, Limb-girdle muscular dystrophy, Muscular dystrophy, congenital, LMNA-related, Lipodystrophy (Dunnigan), Emery-Dreiffus muscular dystrophy, Malouf syndrome, Dilated cardiomyopathy (DCM), Mandibuloacral dysplasia type A, Progeria Hutchinson-Gilford type AD/AR 250 564
LRSAM1 Charcot-Marie-Tooth disease AD/AR 15 14
MARS Interstitial lung and liver disease, Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease, axonal, type 2U AD/AR 9 13
MCM3AP Charcot-Marie-Tooth neuropathy AR 8 19
MED25 Basel-Vanagait-Smirin-Yosef syndrome, Charcot-Marie-Tooth disease AR 4 5
MFN2 Hereditary motor and sensory neuropathy, Charcot-Marie-Tooth disease AD/AR 70 223
MME Spinocerebellar ataxia 43, Charcot-Marie-Tooth disease, axonal, type 2T AD/AR 14 21
MORC2 Charcot-Marie-Tooth disease type, axonal, type 2Z AD 6 17
MPZ Neuropathy, Roussy-Levy syndrome, Dejerine-Sottas disease, Charcot-Marie-Tooth disease AD 108 241
MTMR2 Charcot-Marie-Tooth disease AR 13 23
MYOT Myopathy, myofibrillar, Muscular dystrophy, limb-girdle, 1A, Myopathy, spheroid body AD 6 16
NDRG1 Charcot-Marie-Tooth disease AR 6 8
NEFH* Charcot-Marie-Tooth disease, axonal, type 2CC AD/AR 4 21
NEFL Charcot-Marie-Tooth disease AD 24 40
NGF Neuropathy, hereditary sensory and autonomic AR 2 6
NTRK1 Insensitivity to pain, congenital, with anhidrosis, Medullary thyroid carcinoma, familial AR 38 123
PDK3 Charcot-Marie-Tooth disease XL 1 3
PLEKHG5 Spinal muscular atrophy, Charcot-Marie-Tooth disease AR 16 8
PMP22 Neuropathy, inflammatory demyelinating, Roussy-Levy syndrome, Dejerine-Sottas disease, Neuropathy, hereditary, with liability to pressurve palsies, Charcot-Marie-Tooth disease AD/AR 49 165
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 89 290
PRDM12 Neuropathy, hereditary sensory and autonomic, type VIII AR 7 11
PRPS1* Phosphoribosylpyrophosphate synthetase I superactivity, Arts syndrome, Charcot-Marie-Tooth disease, X-linked recessive, 5, Deafness, X-linked 1 XL 27 32
PRX Dejerine-Sottas disease, Charcot-Marie-Tooth disease AR 26 55
RAB7A Charcot-Marie-Tooth disease AD 5 7
REEP1 Spastic paraplegia, Distal hereditary motor neuronopathy AD 16 60
SACS Spastic ataxia, Charlevoix-Saguenay AR 254 262
SBF1 Charcot-Marie-Tooth disease AR 5 10
SBF2 Charcot-Marie-Tooth disease AR 25 21
SCN11A Episodic pain syndrome, familial, 3, Neuropathy, hereditary sensory and autonomic, type VII AD 8 20
SCN9A Paroxysmal extreme pain disorder, Small fiber neuropathy, Erythermalgia, primary, Generalized epilepsy with febrile seizures plus, type 7, Insensitivity to pain, congenital, autosomal recessive AD/AR 61 125
SCYL1 Spinocerebellar ataxia, autosomal recessive 21 AR 12 6
SEPT9 Amyotrophy, hereditary neuralgic AD 4 11
SETX Ataxia with oculomotor apraxia, Amyotrophic lateral sclerosis, juvenile, Spinocerebellar ataxia AD/AR 36 210
SH3TC2 Mononeuropathy of the median nerve, Charcot-Marie-Tooth disease AR 63 89
SLC12A6 Agenesis of the corpus callosum with peripheral neuropathy (Andermann syndrome) AD/AR 43 19
SLC25A46 Neuropathy, hereditary motor and sensory, type VIB AR 14 17
SMAD3 Aneurysms-osteoarthritis syndrome, Loeys-Dietz syndrome AD 48 82
SPG11 Spastic paraplegia, Amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease AR 162 274
SPTBN4 Myopathy, congenital, with neuropathy and deafness AR 6 7
SPTLC1* Neuropathy, hereditary sensory and autonomic AD 8 11
SPTLC2 Hereditary sensory and autonomic neuropathy AD 5 14
SURF1 Leigh syndrome, Charcot-Marie-Tooth disease AR 50 101
TFG Spastic paraplegia, Hereditary motor and sensory neuropathy, proximal AR 4 7
TRIM2 Charcot-Marie-Tooth disease AR 5 8
TRPV4 Metatropic dysplasia, Spondyloepiphyseal dysplasia Maroteaux type, Parastremmatic dwarfism, Hereditary motor and sensory neuropathy, Spondylometaphyseal dysplasia Kozlowski type, Spinal muscular atrophy, Charcot-Marie-Tooth disease, Brachyolmia (autosomal dominant type), Familial Digital arthropathy with brachydactyly AD 61 78
TTR Dystransthyretinemic hyperthyroxinemia, Amyloidosis, hereditary, transthyretin-related AD 52 148
TYMP Mitochondrial DNA depletion syndrome AR 84 94
VCP Amyotrophic lateral sclerosis, Inclusion body myopathy with early-onset Paget disease, Charcot-Marie-Tooth disease AD 17 61
WNK1 Neuropathy, hereditary sensory and autonomic, Pseudohypoaldosteronism AD/AR 14 9
YARS Charcot-Marie-Tooth disease AD 6 11
ZFYVE26 Spastic paraplegia 15 AR 63 39

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

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

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

Gene refers to the HGNC approved gene symbol; Inheritance refers to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR), mitochondrial (mi), X-linked (XL), X-linked dominant (XLD) and X-linked recessive (XLR); ClinVar refers to the number of variants in the gene classified as pathogenic or likely pathogenic in this database (ClinVar); HGMD refers to the number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD). The list of associated, gene specific phenotypes are generated from CGD or Mitomap databases.

Non-coding variants covered by Charcot-Marie-Tooth Neuropathy Panel

Gene Genomic location HG19 HGVS RefSeq RS-number
AIFM1 ChrX:129274636 c.697-44T>G NM_004208.3
AIFM1 ChrX:129299753 c.-123G>C NM_004208.3 rs724160014
ATP7A ChrX:77279056 c.2916+2480T>G NM_000052.5
ATP7A ChrX:77287843 c.3294+763C>G NM_000052.5
BSCL2 Chr11:62470032 c.405-11A>G NM_001122955.3
GDAP1 Chr8:75274260 c.579+47A>G NM_018972.2
GJB1 ChrX:70442966 c.-16-576_-16-575insT NM_001097642.2
GJB1 ChrX:70443018 c.-16-524C>G NM_001097642.2
GJB1 ChrX:70443029 c.-16-513T>C/G NM_001097642.2
GJB1 ChrX:70443029 c.-16-513T>C NM_001097642.2 rs1003232768
GJB1 ChrX:70443029 c.-16-513T>G NM_001097642.2
GJB1 ChrX:70443031 c.-16-511G>C NM_001097642.2
GJB1 ChrX:70443099 c.-103C>T NM_000166.5 rs863224971
GJB1 ChrX:70443185 c.-17G>A NM_000166.5
GJB1 ChrX:70443186 c.-17+1G>T NM_000166.5
GJB1 ChrX:70443187 c.-17+2T>C NM_000166.5
GJB1 ChrX:70443539 c.-16-3C>G NM_001097642.2
GJB1 ChrX:70443540 c.-16-2A>G NM_001097642.2
GJB1 ChrX:70443541 c.-16-1G>A NM_001097642.2
GJB1 ChrX:70444424 c.*15C>T NM_001097642.2
HADHB Chr2:26500642 c.442+614A>G NM_000183.2
HADHB Chr2:26500691 c.442+663A>G NM_000183.2
HK1 Chr10:71038447 c.-390-3838G>C NM_033500.2 rs797044964
HK1 Chr10:71038467 c.-390-3818G>C NM_033500.2 rs397514654
HK1 Chr10:71075518 c.27+14901A>G NM_033500.2 rs187500777
HSPB1 Chr7:75931813 c.-217T>C NM_001540.3 rs545738637
IGHMBP2 Chr11:68697719 c.1235+894C>A NM_002180.2
LMNA Chr1:156100609 c.513+45T>G NM_170707.3
LMNA Chr1:156105681 c.937-11C>G NM_170707.3 rs267607645
LMNA Chr1:156107037 c.1608+14G>A NM_170707.3
LMNA Chr1:156107433 c.1609-12T>G NM_170707.3 rs267607582
NTRK1 Chr1:156838278 c.575-19G>A NM_002529.3 rs370828525
NTRK1 Chr1:156843392 c.851-33T>A NM_002529.3 rs80356674
NTRK1 Chr1:156851237 c.2206-12C>A NM_002529.3
NTRK1 Chr1:156851238 c.2206-11G>A NM_002529.3
PMP22 Chr17:15162523 c.79-13T>A NM_000304.3
SEPT9 Chr17:75316275 c.-134G>C NM_006640.4 rs80338760
SH3TC2 Chr5:148406329 c.2873-14T>A NM_024577.3
SH3TC2 Chr5:148422415 c.386-15G>A NM_024577.3
SURF1 Chr9:136220806 c.324-11T>G NM_003172.3 rs375398247
VCP Chr9:35072710 c.-360G>C NM_007126.3

Test Strengths

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

Test Limitations

The following exons are not included in the panel as they are not sufficiently covered with high quality sequence reads: HK1 (NM_001322365:5). Genes with suboptimal coverage in our assay are marked with number sign (#) and genes with partial, or whole gene, segmental duplications in the human genome are marked with an asterisk (*) if they overlap with the UCSC pseudogene regions. Gene is considered to have suboptimal coverage when >90% of the gene's target nucleotides are not covered at >20x with mapping quality score (MQ>20) reads. The technology may have limited sensitivity to detect variants in genes marked with these symbols (please see the Panel content table above).

This test does not detect the following:
  • Complex inversions
  • Gene conversions
  • Balanced translocations
  • Some of the panels include the whole mitochondrial genome but not all (please see the Panel Content section)
  • Repeat expansion disorders unless specifically mentioned
  • Non-coding variants deeper than ±20 base pairs from exon-intron boundary unless otherwise indicated (please see above Panel Content / non-coding variants covered by the panel).
This test may not reliably detect the following:
  • Low level mosaicism in nuclear genes (variant with a minor allele fraction of 14.6% is detected with 90% probability)
  • Stretches of mononucleotide repeats
  • Low level heteroplasmy in mtDNA (>90% are detected at 5% level)
  • Indels larger than 50bp
  • Single exon deletions or duplications
  • Variants within pseudogene regions/duplicated segments
  • Some disease causing variants present in mtDNA are not detectable from blood, thus post-mitotic tissue such as skeletal muscle may be required for establishing molecular diagnosis.

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

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

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

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

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

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

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

Sensitivity % (TP/(TP+FN) Specificity %
Single nucleotide variants 99.89% (99,153/99,266) >99.9999%
Insertions, deletions and indels by sequence analysis
1-10 bps 99.2% (7,745/7,806) >99.9999%
11-50 bps 99.13% (2,524/2,546) >99.9999%
Copy number variants (exon level dels/dups)
1 exon level deletion (heterozygous) 100% (20/20) NA
1 exon level deletion (homozygous) 100% (5/5) NA
1 exon level deletion (het or homo) 100% (25/25) NA
2-7 exon level deletion (het or homo) 100% (44/44) NA
1-9 exon level duplication (het or homo) 75% (6/8) NA
Simulated CNV detection
5 exons level deletion/duplication 98.7% 100.00%
Microdeletion/-duplication sdrs (large CNVs, n=37))
Size range (0.1-47 Mb) 100% (25/25)
The performance presented above reached by Blueprint Genetics high-quality, clinical grade NGS sequencing assay with the following coverage metrics
Mean sequencing depth 143X
Nucleotides with >20x sequencing coverage (%) 99.86%

Performance of Blueprint Genetics Mitochondrial Sequencing Assay.

Sensitivity % Specificity %
Single nucleotide variants
Heteroplasmic (45-100%) 100.0% (50/50) 100.0%
Heteroplasmic (35-45%) 100.0% (87/87) 100.0%
Heteroplasmic (25-35%) 100.0% (73/73) 100.0%
Heteroplasmic (15-25%) 100.0% (77/77) 100.0%
Heteroplasmic (10-15%) 100.0% (74/74) 100.0%
Heteroplasmic (5-10%) 100.0% (3/3) 100.0%
Heteroplasmic (<5%) 50.0% (2/4) 100.0%
All types
Single nucleotide variants n=2026 SNVs
Heteroplasmic (45-100%) 100.0% (1940/1940) 100.0%
Heteroplasmic (35-45%) 100.0% (4/4) 100.0%
Heteroplasmic (25-35%) 100.0% (3/3) 100.0%
Heteroplasmic (15-25%) 100.0% (3/3) 100.0%
Heteroplasmic (10-15%) 100.0% (9/9) 100.0%
Heteroplasmic (5-10%) 92.3% (12/13) 99.98%
Heteroplasmic (<5%) 88.9% (48/54) 99.93%
Insertions and deletions by sequence analysis n=40 indels
Heteroplasmic (45-100%) 1-10bp 100.0% (32/32) 100.0%
Heteroplasmic (5-45%) 1-10bp 100.0% (3/3) 100.0%
Heteroplasmic (<5%) 1-10bp 100.0% (5/5) 99,997%
SIMULATION DATA /(mitomap mutations)
Insertions, and deletions 1-24 bps by sequence analysis; n=17
Homoplasmic (100%) 1-24bp 100.0% (17/17) 99.98%
Heteroplasmic (50%) 100.0% (17/17) 99.99%
Heteroplasmic (25%) 100.0% (17/17) 100.0%
Heteroplasmic (20%) 100.0% (17/17) 100.0%
Heteroplasmic (15%) 100.0% (17/17) 100.0%
Heteroplasmic (10%) 94.1% (16/17) 100.0%
Heteroplasmic (5%) 94.1% (16/17) 100.0%
Copy number variants (separate artifical mutations; n=1500)
Homoplasmic (100%) 500 bp, 1kb, 5 kb 100.0% 100.0%
Heteroplasmic (50%) 500 bp, 1kb, 5 kb 100.0% 100.0%
Heteroplasmic (30%) 500 bp, 1kb, 5 kb 100.0% 100.0%
Heteroplasmic (20%) 500 bp, 1kb, 5 kb 99.7% 100.0%
Heteroplasmic (10%) 500 bp, 1kb, 5 kb 99.0% 100.0%
The performance presented above reached by following coverage metrics at assay level (n=66)
Mean of medians Median of medians
Mean sequencing depth MQ0 (clinical) 18224X 17366X
Nucleotides with >1000x MQ0 sequencing coverage (%) (clinical) 100%
rho zero cell line (=no mtDNA), mean sequencing depth 12X


The target region for each gene includes coding exons and ±20 base pairs from the exon-intron boundary. In addition, the panel includes non-coding and regulatory variants if listed above (Non-coding variants covered by the panel). Some regions of the gene(s) may be removed from the panel if specifically mentioned in the ‘Test limitations” section above. If the test includes the mitochondrial genome the target region gene list contains the mitochondrial genes. The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. Our pipeline is streamlined to maximize sensitivity without sacrificing specificity. We have incorporated a number of reference population databases and mutation databases including, but not limited, to 1000 Genomes Project, gnomAD, ClinVar and HGMD into our clinical interpretation software to make the process effective and efficient. For missense variants, in silico variant prediction tools such as  SIFT, PolyPhen, MutationTaster are used to assist with variant classification. Through our online ordering and statement reporting system, Nucleus, ordering providers have access to the details of the analysis, including patient specific sequencing metrics, a gene level coverage plot and a list of regions with suboptimal coverage (<20X for nuclear genes and <1000X for mtDNA) if applicable. This reflects our mission to build fully transparent diagnostics where ordering providers can easily visualize the crucial details of the analysis process.

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 ACMG guideline 2015.

The final step in the analysis is orthogonal confirmation. Sequence and copy number variants classified as pathogenic, likely pathogenic and variants of uncertain significance (VUS) are confirmed using bi-directional Sanger sequencing by orthogonal methods such as qPCR/ddPCR when they do not meet our stringent NGS quality metrics for a true positive call.

Our clinical statement includes tables for sequencing and copy number variants that include basic variant information (genomic coordinates, HGVS nomenclature, zygosity, allele frequencies, in silico predictions, OMIM phenotypes and classification of the variant). In addition, the statement includes detailed descriptions of the variant, gene and phenotype(s) including the role of the specific gene in human disease, the mutation profile, information about the gene’s variation in population cohorts and detailed information about related phenotypes. We also provide links to the references, abstracts and variant databases used to help ordering providers further evaluate the reported findings if desired. The conclusion summarizes all of the existing information and provides our rationale for the classification of the variant.

Identification of pathogenic or likely pathogenic variants in dominant disorders or their combinations in different alleles in recessive disorders are considered molecular confirmation of the clinical diagnosis. In these cases, family member testing can be used for risk stratification. We do not recommend using variants of uncertain significance (VUS) for family member risk stratification or patient management. Genetic counseling is recommended.

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

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