X-linked Intellectual Disability Panel

Is a 106 gene panel that includes assessment of non-coding variants.

Is ideal for patients with a clinical suspicion of X-linked intellectual disability.

Please note, this panel does not include FMR1 trinucleotide repeat expansion and is not ideal for patients suspected to have Fragile X syndrome.

Analysis methods
  • PLUS
4 weeks
Number of genes
Test code
Panel tier
Tier 2
CPT Code *
81470, 81471
* 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 X-linked Intellectual Disability Panel (test code NE0601):

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

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.

Intellectual disability (ID) is more common in males than females in the general population, presumed to be due to mutations in genes on the X chromosome. X-linked ID accounts for approximately 16% of males with intellectual disability. In addition to karyotype abnormalities and Fragile X syndrome, numerous X-linked genes exist where mutations have been described that result in either syndromic or non‐syndromic ID. Epileptic seizures accompany ID in almost half of these X-linked disorders.This panel allows for systematic screening of X-linked nonsyndromic and syndromic intellectual disability.

Genes in the X-linked Intellectual Disability Panel and their clinical significance

To view complete table content, scroll horizontally.

Gene Associated phenotypes Inheritance ClinVar HGMD
ABCD1* Adrenoleukodystrophy XL 95 663
ACSL4 Intellectual developmental disorder XL 6 7
AFF2 Premature ovarian failure, Mental retardation, X-linked, FRAXE type XL 6 25
AP1S2 Mental retardation, syndromic, Fried (Pettigrew syndrome) XL 11 12
ARHGEF6 Intellectual developmental disorder XL 2 5
ARHGEF9 Epileptic encephalopathy, early infantile XL 10 23
ARX# Lissencephaly, Epileptic encephalopathy, Corpus callosum, agenesis of, with abnormal genitalia, Partington syndrome, Proud syndrome, Hydranencephaly with abnormal genitalia, Intellectual developmental disorder XL 66 93
ATP6AP2 Mental retardation, syndromic, Hedera, Parkinsonism with spasticity XL 3 6
ATP7A Menkes disease, Occipital horn syndrome, Spinal muscular atrophy, distal, X-linked 3 XL 116 354
ATRX Carpenter-Waziri syndrome, Alpha-thalassemia/mental retardation syndrome, Holmes-Gang syndrome, Juberg-Marsidi syndrome, Smith-Fineman-Myers syndrome, Mental retardation-hypotonic facies syndrome XL 65 165
BCOR Microphthalmia, syndromic, Oculofaciocardiodental syndrome XL 40 53
BRWD3 Intellectual developmental disorder XL 9 17
CASK Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia, FG syndrome, Intellectual developmental disorder XL 87 112
CDKL5 Epileptic encephalopathy, early infantile, Rett syndrome, atypical, Angelman-like syndrome XL 312 331
CLCN4 Mental retardation, X-linked 49 XL 21 17
CNKSR2 Epileptic encephalopathy, X-linked mental retardation, Epilepsy and X-linked mental retardation XL 7 6
CUL4B Mental retardation, syndromic, Cabezas XL 23 38
DCX Lissencephaly, Subcortical laminal heterotopia XL 131 142
DDX3X Mental retardation, X-linked 102 XL 84 51
DKC1 Hoyeraal-Hreidarsson syndrome, Dyskeratosis congenita XL 48 74
DLG3 Intellectual developmental disorder XL 11 17
ELK1* Intellectual developmental disorder XL 3
FANCB Fanconi anemia XL 11 21
FGD1 Aarskog-Scott syndrome, Mental retardation, syndromic XL 29 51
FLNA Frontometaphyseal dysplasia, Osteodysplasty Melnick-Needles, Otopalatodigital syndrome type 1, Otopalatodigital syndrome type 2, Terminal osseous dysplasia with pigmentary defects, Periventricular nodular heterotopia 1, Melnick-Needles syndrome, Intestinal pseudoobstruction, neuronal, X-linked/Congenital short bowel syndrome, Cardiac valvular dysplasia, X-linked XL 133 257
FMR1 Premature ovarian failure, Fragile X syndrome, Fragile X tremor/ataxia syndrome XL 13 76
FRMPD4 Mental retardation, X-linked 104 4 6
FTSJ1 Intellectual developmental disorder XL 5 10
GDI1 Intellectual developmental disorder XL 7 11
GK* Glycerol kinase deficiency XL 11 35
GPC3 Simpson-Golabi-Behmel syndrome XL 33 75
GRIA3 Intellectual developmental disorder XL 12 23
HCCS Linear skin defects with multiple congenital anomalies 1 (MIDAS syndrome) XL 7 13
HDAC8 Cornelia de Lange syndrome XL 41 50
HPRT1 Lesch-Nyhan syndrome, Kelley-Seegmiller syndrome XL 72 427
HSD17B10 17-beta-hydroxysteroid dehydrogenase X deficiency, Mental retardation, syndromic XL 10 15
HUWE1 Mental retardation, syndromic, Turner XL 37 54
IDS* Mucopolysaccharidosis XL 85 637
IGBP1 Corpus callosum, agenesis of, with mental retardation, ocular coloboma and micrognathia XL 1 2
IL1RAPL1 Intellectual developmental disorder XL 17 41
IQSEC2 Intellectual developmental disorder XL 55 56
KDM5C Mental retardation, syndromic, Claes-Jensen XL 47 55
KIAA2022 Intellectual developmental disorder XL 42 40
KLF8 Intellectual developmental disorder XL 1 2
L1CAM Mental retardation, aphasia, shuffling gait, and adducted thumbs (MASA) syndrome, Hydrocephalus due to congenital stenosis of aqueduct of Sylvius, Spastic, CRASH syndrome, Corpus callosum, partial agenesis XL 80 292
LAMP2 Danon disease XL 62 101
MAGT1 Immunodeficiency, with magnesium defect, Epstein-Barr virus infection and neoplasia, Mental retardation, X-linked 95 XL 8 14
MAOA Brunner syndrome XL 7 14
MBTPS2 Keratosis follicularis spinulosa decalvans, IFAP syndrome, Palmoplantar keratoderma, mutilating, with periorificial keratotic plaques XL 12 25
MECP2 Angelman-like syndrome, Autism, Rett syndrome, Encephalopathy, Intellectual developmental disorder XL 506 1039
MED12 Ohdo syndrome, Intellectual disability with Marfanoid habitus, FG syndrome, Opitz-Kaveggia syndrome, Lujan-Fryns syndrome XL 29 30
MID1* Opitz GBBB syndrome XL 30 96
MSL3 Mental retardation, X-linked XL 9
MTM1 Myopathy, centronuclear XL 158 301
NDP Exudative vitreoretinopathy, Norrie disease XL 31 167
NDUFA1 Mitochondrial complex I deficiency XL 3 4
NHS Nance-Horan syndrome, Cataract XL 36 52
NLGN3 Autism, Asperger syndrome XL 2 10
NLGN4X Autism, Asperger syndrome, Intellectual developmental disorder XL 7 35
NONO Mental retardation, X-linked, syndrome 34, Left ventricular non-compaction cardiomyopathy (LVNC) XL 10 4
NSDHL Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD syndrome), CK syndrome XL 15 28
NXF5#* Familial heart block and focal segmental glomerulosclerosis, Mental retardation, syndromic, X-linked XL 5
OCRL Lowe syndrome, Dent disease XL 47 264
OFD1 Simpson-Golabi-Behmel syndrome, Retinitis pigmentosa, Orofaciodigital syndrome, Joubert syndrome XL 153 160
OPHN1 Mental retardation, with cerebellar hypoplasia and distinctive facial appearance XL 28 42
OTC Ornithine transcarbamylase deficiency XL 343 513
PAK3 Intellectual developmental disorder XL 9 13
PCDH19 Epileptic encephalopathy, early infantile XL 116 200
PDHA1 Leigh syndrome, Pyruvate dehydrogenase E1-alpha deficiency XL 66 192
PGK1 Phosphoglycerate kinase 1 deficiency XL 16 26
PHF6 Borjeson-Forssman-Lehmann syndrome XL 22 29
PHF8 Mental retardation syndrome, Siderius XL 13 15
PLP1 Spastic paraplegia, Pelizaeus-Merzbacher disease XL 60 348
PORCN Focal dermal hypoplasia XL 16 121
PQBP1 Renpenning syndrome XL 14 18
PRPS1* Phosphoribosylpyrophosphate synthetase I superactivity, Arts syndrome, Charcot-Marie-Tooth disease, X-linked recessive, 5, Deafness, X-linked 1 XL 27 32
PTCHD1 Autism susceptibility, X-linked 4 XL 9 47
RAB39B Waisman parkinsonism-mental retardation syndrome, Intellectual developmental disorder XL 6 17
RBM10 TARP syndrome XL 12 10
RLIM* Mental retardation, X-linked 61 XL 4 5
RPL10 Autism XL 4 5
RPS6KA3 Coffin-Lowry syndrome, Intellectual developmental disorder XL 65 171
SHROOM4 Stocco dos Santos mental retardation syndrome XL 4 9
SLC16A2 Allan-Herndon-Dudley syndrome XL 39 84
SLC6A8* Creatine deficiency syndrome XL 38 133
SLC9A6 Mental retardation, syndromic, Christianson XL 24 28
SMC1A Cornelia de Lange syndrome XL 73 87
SMS Mental retardation, Snyder-Robinson XL 11 14
SOX3 Panhypopituitarism XL 4 26
SRPX2 ?Rolandic epilepsy, impaired intellectual development, and speech dyspraxia XL 3 4
SYN1 Epilepsy, with variable learning disabilities and behavior disorders XL 12 8
SYP Intellectual developmental disorder XL 4 8
TAF1 Dystonia 3, torsion, X-linked, Mental retardation, X-linked, syndromic 33 XL 13 14
THOC2 Mental retardation, X-linked 12, Arthrogryposis multiplex congenita XL 12 5
TIMM8A* Mohr-Tranebjaerg syndrome, Jensen syndrome, Opticoacoustic nerve atrophy with dementia XL 11 21
TSPAN7 Intellectual developmental disorder XL 4 12
UBE2A Mental retardation, syndromic, Nascimento XL 9 25
UPF3B Mental retardation, syndromic XL 9 21
USP9X Mental retardation, X-linked 99, Mental retardation, X-linked 99, syndromic, female restricted XL 30 27
ZC4H2 Wieacker-Wolff syndrome XL 20 16
ZCCHC12 Intellectual developmental disorder XL 2
ZDHHC9 Mental retardation, syndromic, Raymond XL 9 14
ZNF41 Intellectual developmental disorder XL 6
ZNF674 Intellectual developmental disorder XL 7
ZNF711 Intellectual developmental disorder XL 6 8
ZNF81 Intellectual developmental disorder XL 3 3

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


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

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

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

Non-coding variants covered by X-linked Intellectual Disability Panel

To view complete table content, scroll horizontally.

Gene Genomic location HG19 HGVS RefSeq RS-number
ARHGEF6 ChrX:135861667 c.166-11T>C NM_004840.2 rs140322310
ATP7A ChrX:77279056 c.2916+2480T>G NM_000052.5
ATP7A ChrX:77287843 c.3294+763C>G NM_000052.5
CDKL5 ChrX:18525053 c.-162-2A>G NM_003159.2 rs786204973
DKC1 ChrX:153991099 c.-142C>G NM_001363.3 rs199422241
DKC1 ChrX:153991100 c.-141C>G NM_001363.3
DKC1 ChrX:153993704 c.85-15T>C NM_001363.3
DLG3 ChrX:69665038 c.-8dupG NM_021120.3
FGD1 ChrX:54476768 c.2016-35delA NM_004463.2
FLNA ChrX:153581587 c.6023-27_6023-16delTGACTGACAGCC NM_001110556.1
FMR1 ChrX:147031110 c.*746T>C NM_002024.5 rs183130936
GK ChrX:30688489 c.259+2254G>A NM_001205019.1
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:148568762 c.*57A>G NM_006123.4
IDS ChrX:148578704 c.709-657G>A NM_000202.5
IGBP1 ChrX:69353741 c.-57_-55delTATinsAA NM_001551.2
L1CAM ChrX:153128846 c.3531-12G>A NM_000425.4
L1CAM ChrX:153131293 c.2432-19A>C NM_000425.4
L1CAM ChrX:153133652 c.1704-75G>T NM_000425.4
L1CAM ChrX:153133926 c.1547-14delC NM_000425.4
L1CAM ChrX:153136500 c.523+12C>T NM_000425.4
MTM1 ChrX:149767035 c.137-19_137-16delACTT NM_000252.2
MTM1 ChrX:149767045 c.137-11T>A NM_000252.2
MTM1 ChrX:149783032 c.232-26_232-23delGACT NM_000252.2
MTM1 ChrX:149808833 c.529-909A>G NM_000252.2
MTM1 ChrX:149818176 c.868-13T>A NM_000252.2
NDP ChrX:43818099 c.-207-1G>A NM_000266.3
NDP ChrX:43832545 c.-208+5G>A NM_000266.3
NDP ChrX:43832548 c.-208+2T>G NM_000266.3
NDP ChrX:43832549 c.-208+1G>A NM_000266.3
NDP ChrX:43832685 c.-343A>G NM_000266.3 rs895911086
NDP ChrX:43832722 c.-391_-380delCTCTCTCTCCCTinsGTCTCTC NM_000266.3
NDP ChrX:43832724 c.-396_-383delTCCCTCTCTCTCTC NM_000266.3 rs770996360
NSDHL ChrX:152037789 c.*129C>T NM_015922.2 rs145978994
OCRL ChrX:128674707 c.40-14A>G NM_000276.3
OCRL ChrX:128687279 c.239-4023A>G NM_000276.3
OCRL ChrX:128696350 c.940-11G>A NM_000276.3
OFD1 ChrX:13768358 c.935+706A>G NM_003611.2 rs730880283
OFD1 ChrX:13773245 c.1130-22_1130-19delAATT NM_003611.2 rs312262865
OFD1 ChrX:13773249 c.1130-20_1130-16delTTGGT NM_003611.2
OTC ChrX:38202566 c.-9384G>T NM_000531.5
OTC ChrX:38211584 NM_000531.5 rs191615506
OTC ChrX:38211793 c.-157T>G NM_000531.5
OTC ChrX:38211808 c.-142G>A NM_000531.5
OTC ChrX:38211811 c.-139A>G NM_000531.5
OTC ChrX:38211834 c.-116C>T NM_000531.5
OTC ChrX:38211835 c.-115C>T NM_000531.5
OTC ChrX:38211844 c.-106C>A NM_000531.5 rs749748052
OTC ChrX:38260946 c.540+265G>A NM_000531.5
OTC ChrX:38269404 c.867+1126A>G NM_000531.5
OTC ChrX:38272343 c.1005+1091C>G NM_000531.5
PDHA1 ChrX:19371182 c.533-17_533-14delTGTT NM_001173454.1
PDHA1 ChrX:19372579 c.625-30G>A NM_001173454.1
PDHA1 ChrX:19373648 c.873+26G>A NM_001173454.1
PDHA1 ChrX:19377849 c.*79_*90dupAGTCAATGAAAT NM_001173454.1 rs606231192
PDHA1 ChrX:19377861 c.*79_*90dupAGTCAATGAAAT NM_001173454.1
PGK1 ChrX:77381262 c.1214-25T>G NM_000291.3
PLP1 ChrX:103031997 c.4+78_4+85delGGGGGTTC NM_000533.3
PLP1 ChrX:103041680 c.453+28_453+46delTAACAAGGGGTGGGGGAAA NM_000533.3
PLP1 ChrX:103042405 c.454-322G>A NM_000533.3
PLP1 ChrX:103042413 c.454-314T>A/G NM_000533.3
PLP1 ChrX:103042413 c.454-314T>G NM_000533.3
PLP1 ChrX:103042413 c.454-314T>A NM_000533.3
PORCN ChrX:48370668 c.374-46T>A NM_203475.1
PORCN ChrX:48370699 c.374-15G>A NM_203475.1
RPS6KA3 ChrX:20191268 c.1228-279T>G NM_004586.2
RPS6KA3 ChrX:20213274 c.326-11A>G NM_004586.2
TAF1 ChrX:70749635 rs397509359
TIMM8A ChrX:100601671 c.133-23A>C NM_004085.3 rs869320666

Test Strengths

The strengths of this test include:

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

Test Limitations

This panel does not cover repeat expansion variants such as (CGG)n repeat expansion in *FMR1* causing Fragile X syndrome. Genes with suboptimal coverage in our assay are marked with number sign (#) and genes with partial, or whole gene, segmental duplications in the human genome are marked with an asterisk (*) if they overlap with the UCSC pseudogene regions. Gene is considered to have suboptimal coverage when >90% of the gene’s target nucleotides are not covered at >20x with mapping quality score (MQ>20) reads. The technology may have limited sensitivity to detect variants in genes marked with these symbols (please see the Panel content table above).

This test does not detect the following:

  • Complex inversions
  • Gene conversions
  • Balanced translocations
  • Some of the panels include the whole mitochondrial genome but not all (please see the Panel Content section)
  • Repeat expansion disorders unless specifically mentioned
  • Non-coding variants deeper than ±20 base pairs from exon-intron boundary unless otherwise indicated (please see above Panel Content / non-coding variants covered by the panel).

This test may not reliably detect the following:

  • Low level mosaicism in nuclear genes (variant with a minor allele fraction of 14.6% is detected with 90% probability)
  • Stretches of mononucleotide repeats
  • Low level heteroplasmy in mtDNA (>90% are detected at 5% level)
  • Indels larger than 50bp
  • Single exon deletions or duplications
  • Variants within pseudogene regions/duplicated segments
  • Some disease causing variants present in mtDNA are not detectable from blood, thus post-mitotic tissue such as skeletal muscle may be required for establishing molecular diagnosis.

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

For additional information, please refer to the Test performance section.

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

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

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

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

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

Sensitivity % (TP/(TP+FN) Specificity %
Single nucleotide 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.

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 cornerstone 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 or by orthogonal methods such as qPCR/ddPCR when they do not meet our stringent NGS quality metrics for a true positive call.

Our clinical 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 healthcare provider at no additional cost, according to our latest follow-up reporting policy.