Retinitis Pigmentosa Panel

  • Is a 116 gene panel that includes assessment of non-coding variants
  • Is ideal for patients with a clinical suspicion /diagnosis of isolated retinitis pigmentosa. The genes included on this panel are included in the Retinal Dystrophy Panel.

    For patients with syndromic retinitis pigmentosa, we recommend the Retinal Dystrophy Panel.

Analysis methods
  • PLUS

4 weeks

Number of genes


Test code


Panel size


CPT codes


The Blueprint Genetics Retinitis Pigmentosa Panel (test code OP0901):

Test Specific Strength

The majority of the X-linked RP is caused by mutations in theRPGR gene, which contains a mutational hotspot at a unique 567-aa exon called ORF15 accounting for two-thirds of all disease-causing mutations. The exon ORF15, however, includes a highly repetitive, purine-rich sequence, which generally performs poorly in NGS-based assays. Blueprint Genetics custom assay has good coverage (>20x) with high mapping rates (mapping quality >20) for 100.0% of the target regions in RPGR gene. Our validation showed high mean coverage of 139X for the RPGR gene. Thus, our NGS Panel is not expected to have major limitations in detecting variants in RPGR gene including ORF15 exon.

ICD codes

Commonly used ICD-10 code(s) when ordering the Retinitis Pigmentosa Panel

ICD-10 Disease
H35.50 Stargardt disease
Q14.1 X-linked retinoschisis
H35.50 Retinitis pigmentosa
H31.21 Choroideremia
E72.4 Gyrate atrophy of choroid and retina

Sample Requirements

  • Blood (min. 1ml) in an EDTA tube
  • Extracted DNA, min. 2 μg in TE buffer or equivalent
  • Saliva (Oragene DNA OG-500 kit/OGD-500 or OG-575 & OGD-575)

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

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue. Read more about our sample requirements here.

Please include fundus photographs, electroretinogram (ERG) findings, visual field findings and visual acuity, if available, for expert review and clinical correlation with test results

Retinitis pigmentosa (RP) is a group of inherited disorders in which abnormalities of the photoreceptors (rods and cones) or the retinal pigment epithelium lead to progressive visual loss. RP can be isolated or syndromic. Nonsyndromic RP is extremely heterogeneous, both clinically and genetically, and it may be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Autosomal dominant RP is estimated to account for 15-25% of cases, autosomal recessive RP for 5-20% and X-linked 5-15% (GeneReviews). Sporadic cases are common (40-50%). Severity is partly correlated with the pattern of inheritance with X-linked cases having the most severe course. The major causative genes are USH2A, which is implicated in autosomal recessive RP, RHO, accounting for approximately 28% of autosomal dominant RP and RPGR, which is estimated to explain 70% of X-linked RP. The prevalence of RP is reported to be 1:4,000 to 1:5,000.

Genes in the Retinitis Pigmentosa Panel and their clinical significance

Gene Associated phenotypes Inheritance ClinVar HGMD
ABCA4 Stargardt disease, Retinitis pigmentosa, Cone rod dystrophy, Retinal dystrophy, early-onset severe, Fundus flavimaculatus AR 308 1231
ABHD12 Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract AR 16 20
ADIPOR1* Complement system AD/AR 4
AGBL5 Retinitis pigmentosa 75 AR 2 9
AHI1 Joubert syndrome AR 62 93
AIPL1 Retinitis pigmentosa, Cone rod dystrophy, Leber congenital amaurosis AD/AR 10 79
ARHGEF18 Retinitis pigmentosa 78 AR 5 6
ARL2BP Retinitis pigmentosa with or without situs inversus AR 4 4
ARL3 Retinitis pigmentosa AD 1
ARL6 Bardet-Biedl syndrome, Retinitis pigmentosa AR 14 21
BBS1 Bardet-Biedl syndrome AR 66 103
BBS2 Bardet-Biedl syndrome, Retinitis pigmentosa AR 58 91
BEST1 Vitreoretinochoroidopathy, Microcornea, Rod-cone dystrophy, Posterior staphyloma, Bestrophinopathy, Vitelliform macular dystrophy, Cataract, Retinitis pigmentosa, Macular dystrophy, vitelliform, adult-onset, Retinitis pigmentosa 50, Macular dystrophy, vitelliform 2, Best macular dystrophy, Bestrophinopathy, autosomal recessive AD/AR 62 318
C1QTNF5 Late-onset retinal degeneration AD 27 7
C21ORF2 Retinal dystrophy with or without macular staphyloma (RDMS), Spondylometaphyseal dysplasia, axial (SMDAX) AR 13 22
C2ORF71 Retinitis pigmentosa AR 17 51
C8ORF37 Retinitis pigmentosa, Cone rod dystrophy AR 8 17
CA4 Retinitis pigmentosa 17 AD 3 10
CDHR1 Retinitis pigmentosa, Cone rod dystrophy AR 12 48
CEP290* Bardet-Biedl syndrome, Leber congenital amaurosis, Joubert syndrome, Senior-Loken syndrome, Meckel syndrome AR 130 289
CERKL Retinitis pigmentosa AR 20 37
CHM# Choroideremia XL 46 284
CLN3 Neuronal ceroid lipofuscinosis, type 3 AR 100 72
CLRN1 Retinitis pigmentosa, Usher syndrome, type IV AR 24 39
CNGA1# Retinitis pigmentosa AR 14 33
CNGB1 Retinitis pigmentosa AR 25 61
CRB1 Retinitis pigmentosa, Pigmented paravenous chorioretinal atrophy, Leber congenital amaurosis AR 54 334
CRX Cone rod dystrophy, Leber congenital amaurosis AD/AR 30 106
CTNNA1 Macular dystrophy, patterned 2 AD 6 10
CWC27 Retinitis pigmentosa with or without skeletal anomalies (RPSKA) AR 5 7
CYP4V2 Retinitis pigmentosa, Bietti crystalline corneoretinal dystrophy AR 31 94
DHDDS Retinitis pigmentosa AR 5 8
DHX38 Retinitis pigmentosa AR 1
EYS* Retinitis pigmentosa AR 97 321
FAM161A Retinitis pigmentosa AR 14 20
FLVCR1 Ataxia, posterior column, with retinitis pigmentosa AR 9 15
GNPTG Mucolipidosis AR 45 46
GUCY2D Cone rod dystrophy, Leber congenital amaurosis AD/AR 34 235
HGSNAT Mucopolysaccharidosis (Sanfilippo syndrome), Retinitis pigmentosa AR 43 72
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
IDH3A Leber congenital amaurosis 7
IDH3B Retinitis pigmentosa AR 2 3
IFT140 Short -rib thoracic dysplasia with or without polydactyly, Asphyxiating thoracic dysplasia (ATD; Jeune) AR 38 63
IMPDH1 Retinitis pigmentosa, Leber congenital amaurosis AD 7 23
IMPG2 Retinitis pigmentosa, Vitelliform macular dystrophy AD/AR 25 40
INPP5E Joubert syndrome, Mental retardation, truncal obesity, retinal dystrophy, and micropenis (MORM syndrome) AR 25 50
KIAA1549 Retinitis pigmentosa AR 1 6
KIZ Retinitis pigmentosa 69 AR 3 4
KLHL7 Retinitis pigmentosa, Retinitis pigmentosa 42, Cold-induced sweating syndrome 3 AD/AR 12 11
LCA5 Leber congenital amaurosis AR 10 49
LRAT Retinitis pigmentosa, juvenile, Leber congenital amaurosis, Retinitis punctata albescens, Retinal-dystrophy, early-onset severe AR 8 23
MAK Retinitis pigmentosa AR 11 22
MERTK Retinitis pigmentosa AR 25 75
MFRP Microphthalmia, isolated 5, Nanophthalmos 2, Retinitis pigmentosa, autosomal recessive AR 27 30
MVK Mevalonic aciduria, Hyper-IgD syndrome, Porokeratosis 3, multiple types AD/AR 35 181
NEK2# Retinitis pigmentosa 67 AR 1 1
NMNAT1# Leber congenital amaurosis AR 20 74
NR2E3 Retinitis pigmentosa, Enhanced S-cone syndrome AD/AR 19 77
NRL Retinitis pigmentosa, Clumped pigmentary retinal degeneration AD/AR 11 25
OAT Gyrate atrophy of choroid and retina AR 67 71
OFD1 Simpson-Golabi-Behmel syndrome, Retinitis pigmentosa, Orofaciodigital syndrome, Joubert syndrome XL 153 160
PDE6A Retinitis pigmentosa AR 16 49
PDE6B Retinitis pigmentosa, Night blindness, congenital stationary AD/AR 35 125
PDE6G Retinitis pigmentosa AR 1 2
PEX1 Heimler syndrome, Peroxisome biogenesis factor disorder 1A, Peroxisome biogenesis factor disorder 1B AR 112 134
PEX2 Zellweger syndrome, Peroxisome biogenesis disorder AR 16 18
PEX7 Refsum disease, Rhizomelic CDP type 1 AR 44 53
PHYH Refsum disease AR 12 36
PITPNM3 Cone-rod dystrophy 5 AD 1 5
PLA2G5 Fleck retina, familial benign AR 1 7
POMGNT1 Muscular dystrophy-dystroglycanopathy AR 96 88
PRCD Retinitis pigmentosa AR 2 7
PROM1 Stargardt disease, Retinitis pigmentosa, Cone rod dystrophy, Macular dystrophy, retinal, AD/AR 22 80
PRPF3 Retinitis pigmentosa AD 3 7
PRPF31 Retinitis pigmentosa AD 36 165
PRPF4 Retinitis pigmentosa 70 AD 2 4
PRPF6 Retinitis pigmentosa 60 AD 4 11
PRPF8 Retinitis pigmentosa AD 13 46
PRPH2 Choriodal dystrophy, central areolar, Macular dystrophy, vitelliform, Retinitis pigmentosa, Retinitis punctata albescens, Macula dystrophy, patterned AD/AR 48 176
RBP3 Retinitis pigmentosa AR 5 17
RBP4 Retinal dystrophy, iris coloboma, and comedogenic acne syndrome, Microphthalmia, isolated, with coloboma 10 AD/AR 8 7
RCBTB1 Retinal dystrophy with or without extraocular anomalies (RDEOA), Familial exudative vitreoretinopathy 6 9
RDH12 Retinitis pigmentosa, Leber congenital amaurosis AD/AR 23 102
RDH5 Fundus albipunctatus AR 11 51
REEP6 Retinitis pigmentosa 77 AR 4 8
RGR Retinitis pigmentosa AD/AR 2 11
RHO Retinitis pigmentosa, Night blindness, congenital stationary, Retinitis punctata albescens AD/AR 58 212
RIMS1 Cone-rod dystrophy 7 AD 3 12
RLBP1 Newfoundland rod-cone dystrophy, Fundus albipunctatus, Bothnia retinal dystrophy, Retinitis punctata albescens AR 9 37
ROM1 Retinitis pigmentosa 7, digenic Digenic 3 18
RP1 Retinitis pigmentosa AD/AR 45 181
RP2 Retinitis pigmentosa XL 26 118
RPE65 Retinitis pigmentosa, Leber congenital amaurosis AR 31 197
RPGR Retinitis pigmentosa, Cone-rod dystrophy, X-linked, 1, Macular degeneration, X-linked atrophic, Retinitis pigmentosa 3 XL 79 218
RPGRIP1 Cone rod dystrophy, Leber congenital amaurosis AR 44 145
RS1 Retinoschisis XL 44 262
SAG Retinitis pigmentosa, Oguchi disease AD/AR 6 15
SAMD11 Retinitis pigmentosa AR 2 5
SCAPER Retinal dystrophy, Retinitis pigmentosa, Intellectual disability, Bardet-Biedl syndrome AR 4 7
SCLT1# Senior-Loken syndrome, Retinal dystrophy 3
SEMA4A Retinitis pigmentosa, Cone rod dystrophy AR 4 14
SLC7A14 Retinitis pigmentosa 68 AR 4 8
SNRNP200 Retinitis pigmentosa AD 6 34
SPATA7 Leber congenital amaurosis, Retitinitis pigmentosa AR 15 39
SPP2 Retinitis pigmentosa AD 1 2
TOPORS Retinitis pigmentosa AD 7 22
TTC8 Bardet-Biedl syndrome, Retinitis pigmentosa AR 5 16
TTPA Ataxia with isolated vitamin E deficiency AR 29 30
TUB Retinal dystrophy and obesity AR 1 2
TULP1 Retinitis pigmentosa, Leber congenital amaurosis AR 24 74
USH1C Deafness, Usher syndrome, type IV AR 45 51
USH2A Retinitis pigmentosa 39, Usher syndrome, type 2A AR 401 1169
VPS13B Cohen syndrome AR 351 203
WDR19 Retinitis pigmentosa, Nephronophthisis, Short -rib thoracic dysplasia with or without polydactyly, Senior-Loken syndrome, Cranioectodermal dysplasia (Levin-Sensenbrenner) type 1, Cranioectodermal dysplasia (Levin-Sensenbrenner) type 2, Asphyxiating thoracic dysplasia (ATD; Jeune) AR 33 43
ZNF408 Exudative vitreoretinopathy 6, Retinitis pigmentosa 72 AD/AR 3 9
ZNF513 Retinitis pigmentosa AR 1 3

* 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 (#)

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

Non-coding variants covered by Retinitis Pigmentosa Panel

Gene Genomic location HG19 HGVS RefSeq RS-number
ABCA4 Chr1:94461770 c.6730-19G>A NM_000350.2 rs375179475
ABCA4 Chr1:94468019 c.6148-471C>T NM_000350.2
ABCA4 Chr1:94481967 c.5197–557G>T NM_000350.2
ABCA4 Chr1:94484001 c.5196+1137G>A NM_000350.2 rs778234759
ABCA4 Chr1:94484001 c.5196+1137G>T NM_000350.2
ABCA4 Chr1:94484082 c.5196+1056A>G NM_000350.2
ABCA4 Chr1:94492936 c.4539+2065C>G NM_000350.2
ABCA4 Chr1:94492937 c.4539+2064C>T NM_000350.2
ABCA4 Chr1:94492973 c.4539+2028C>T NM_000350.2 rs869320785
ABCA4 Chr1:94493000 c.4539+2001G>A NM_000350.2
ABCA4 Chr1:94493073 c.4539+1928C>T NM_000350.2
ABCA4 Chr1:94493272 c.4539+1729G>T NM_000350.2
ABCA4 Chr1:94493895 c.4539 +1106C>T NM_000350.2
ABCA4 Chr1:94493901 c.4539+1100A>G NM_000350.2
ABCA4 Chr1:94496509 c.4253+43G>A NM_000350.2
ABCA4 Chr1:94508465 c.3191–11T>A NM_000350.2
ABCA4 Chr1:94509047 c.3051-16T>A NM_000350.2
ABCA4 Chr1:94509799 c.3050+370C>T NM_000350.2
ABCA4 Chr1:94510683 c.2919-383C>T NM_000350.2
ABCA4 Chr1:94525509 c.2160+584A>G NM_000350.2
ABCA4 Chr1:94526934 c.1938-619A>G NM_000350.2
ABCA4 Chr1:94527698 c.1937+435C>G NM_000350.2
ABCA4 Chr1:94528120 c.1937+13T>G NM_000350.2
ABCA4 Chr1:94546780 c.859-506G>C NM_000350.2
ABCA4 Chr1:94546814 c.859–540C>G NM_000350.2
ABCA4 Chr1:94549781 c.769–784C>T NM_000350.2
ABCA4 Chr1:94561127 c.768+3223C>T NM_000350.2
ABCA4 Chr1:94566773 c.570+1798A>G NM_000350.2
ABCA4 Chr1:94576926 c.302+68C>T NM_000350.2 rs761188244
ABCA4 Chr1:94577158 c.161–23T>G NM_000350.2
ABCA4 Chr1:94578638 c.67-16T>A NM_000350.2
ABCA4 Chr14:21793564 c.2367+23delG NM_020366.3
BBS1 Chr11:66291105 c.951+58C>T NM_024649.4
BEST1 Chr11:61717900 c.-29+1G>T NM_001139443.1
BEST1 Chr11:61717904 c.-29+5G>A NM_001139443.1
C21ORF2 Chr21:45750232 c.1000-23A>T NM_001271441.1
CEP290 Chr12:88462434 c.6012-12T>A NM_025114.3 rs752197734
CEP290 Chr12:88494960 c.2991+1655A>G NM_025114.3 rs281865192
CEP290 Chr12:88508350 c.1910-11T>G NM_025114.3
CEP290 Chr12:88534822 c.103-18_103-13delGCTTTT NM_025114.3
CHM ChrX:85220593 c.315-1536A>G NM_000390.2
CHM ChrX:85223644 c.315-4587T>A NM_000390.2
CHM ChrX:85302626 NM_000390.2
CHM ChrX:85302634 NM_000390.2
CHM ChrX:85302634 NM_000390.2
CHM ChrX:85302644 NM_000390.2
CLN3 Chr16:28493392 c.1056+34C>A NM_000086.2
CLN3 Chr16:28497984 c.461-13G>C NM_000086.2 rs386833721
CLRN1 Chr3:150660197 c.254-649T>G NM_001195794.1 rs976853535
DHDDS Chr1:26774026 c.441-24A>G NM_024887.3 rs764831063
EYS Chr6:66417023 c.-448+5G>A NM_001142800.1
GNPTG Chr16:1412562 c.610-16_609+28del NM_032520.4 rs193302853
GUCY2D Chr17:7906220 c.-9-137T>C NM_000180.3
HGSNAT Chr8:43028824 c.821-28_821-10delTTGCTTATGCTTTGTACTT NM_152419.2
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
IFT140 Chr16:1576595 c.2577+25G>A NM_014714.3 rs1423102192
LRAT Chr4:155670121 c.541-15T>G NM_004744.3 rs779487944
MVK Chr12:110029032 c.769-7dupT NM_000431.2 rs104895348
NMNAT1 Chr1:10003560 c.-70A>T NM_022787.3
NMNAT1 Chr1:10003561 c.-69C>T NM_022787.3
NMNAT1 Chr1:10003580 c.-57+7T>G NM_022787.3
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
PEX7 Chr6:137143759 c.-45C>T NM_000288.3 rs267608252
PROM1 Chr4:15989860 c.2077-521A>G NM_006017.2 rs796051882
PRPF31 Chr19:54631586 c.1073+20_1073+36delCGGTAGGCATGGGGGTC NM_015629.3
PRPF31 Chr19:54633399 c.1374+654C>G NM_015629.3
PRPF4 Chr9:116037909 NM_004697.4 rs541873609
RDH5 Chr12:56114302 c.-33+2dupT NM_002905.3
RPE65 Chr1:68910577 c.246-11A>G NM_000329.2
RPGR ChrX:38128234 NM_000328.2
RPGR ChrX:38160137 c.1059+363G>A NM_001034853.1
RPGRIP1 Chr14:21789155 c.1468-263G>C NM_020366.3
RPGRIP1 Chr14:21789588 c.1611+27G>A NM_020366.3
RPGRIP1 Chr14:21793563 c.2367+23delG NM_020366.3 rs781728563
RPGRIP1 Chr14:21795769 c.2711-13G>T NM_020366.3 rs369991630
USH2A Chr1:215821092 c.14583-20C>G NM_206933.2
USH2A Chr1:215967783 c.9959-4159A>G NM_206933.2
USH2A Chr1:216039721 c.8845+628C>T NM_206933.2
USH2A Chr1:216064540 c.7595-2144A>G NM_206933.2 rs786200928
USH2A Chr1:216247476 c.5573-834A>G NM_206933.2
USH2A Chr1:216592035 c.486-14G>A NM_206933.2 rs374536346
USH2A Chr1:216596610 c.-259G>T NM_206933.2

Added and removed genes from the panel

Genes added Genes removed

Test Strengths

The majority of the X-linked RP is caused by mutations in theRPGR gene, which contains a mutational hotspot at a unique 567-aa exon called ORF15 accounting for two-thirds of all disease-causing mutations. The exon ORF15, however, includes a highly repetitive, purine-rich sequence, which generally performs poorly in NGS-based assays. Blueprint Genetics custom assay has good coverage (>20x) with high mapping rates (mapping quality >20) for 100.0% of the target regions in RPGR gene. Our validation showed high mean coverage of 139X for the RPGR gene. Thus, our NGS Panel is not expected to have major limitations in detecting variants in RPGR gene including ORF15 exon.

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
  • 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: CHM (NM_001145414:5), CNGA1 (NM_001142564:2), HK1 (NM_001322365:5), NEK2 (NM_001204182:8), NMNAT1 (NM_001297779:5), SCLT1 (NM_001300898:6). 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
  • Mitochondrial DNA variants
  • Repeat expansion disorders unless specifically mentioned
  • Non-coding variants deeper than ±20 base pairs from exon-intron boundary unless otherwise indicated (please see above Panel Content / non-coding variants covered by the panel).
This test may not reliably detect the following:
  • Low level mosaicism (variant with a minor allele fraction of 14.6% is detected with 90% probability)
  • Stretches of mononucleotide repeats
  • Indels larger than 50bp
  • Single exon deletions or duplications
  • Variants within pseudogene regions/duplicated segments

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

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

The 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.

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 96.9% (7,563/7,806) >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% (37/37)
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%


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. 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 <20X sequencing depth 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 Blueprint Genetics Variant Classification Schemes based on the ACMG guideline 2015. Minor modifications were made to increase reproducibility of the variant classification and improve the clinical validity of the report. Our experience with tens of thousands of clinical cases analyzed at our laboratory allowed us to further develop the industry standard.

The final step in the analysis is orthogonal confirmation. Sequence variants classified as pathogenic, likely pathogenic and variants of uncertain significance (VUS) are confirmed using bi-directional Sanger sequencing when they do not meet our stringent NGS quality metrics for a true positive call.
Reported heterozygous and homo/hemizygous copy number variations with a size <10 and <3 target exons are confirmed by orthogonal methods such as qPCR if the specific CNV has been seen and confirmed less than three times at Blueprint Genetics.

Our clinical statement includes tables for sequencing and copy number variants that include basic variant information (genomic coordinates, HGVS nomenclature, zygosity, allele frequencies, in silico predictions, OMIM phenotypes and classification of the variant). In addition, the statement includes detailed descriptions of the variant, gene and phenotype(s) including the role of the specific gene in human disease, the mutation profile, information about the gene’s variation in population cohorts and detailed information about related phenotypes. We also provide links to the references, 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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