Blueprint Genetics / Tests / Panels / Ophthalmology / Retinal Dystrophy Panel

Retinal Dystrophy Panel

Summary
Is a 351 gene panel that includes assessment of non-coding variants.

In addition, it also includes the maternally inherited mitochondrial genome.
Is ideal for patients with a clinical suspicion / diagnosis of an isolated or syndromic retinal dystrophy.

Is not ideal for patients suspected to have blue cone monochromacy, caused by variants in the OPN1LW and OPN1MW genes.

For patients in the USA with an inherited retinal degenerative disease, please visit the no-cost My Retina Tracker Program for further details.

Analysis methods
  • PLUS
Availability
4 weeks
Number of genes
351
Test code
OP0801
Panel tier
Tier 3
CPT Code *
81434, 81460, 81465
* 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.

Summary

The Blueprint Genetics Retinal Dystrophy Panel (test code OP0801):

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

The majority of the X-linked RP is caused by mutations in the*RPGR* 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

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.

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

Subpanel Description

This comprehensive panel includes genes from the following panels: Achromatopsia, Macular Dystrophy, Leber Congenital Amaurosis, Congenital Stationary Night Blindness, Flecked Retina Disorders, Vitreoretinopathy, Cone Rod Dystrophy, Retinitis Pigmentosa, Usher Syndrome, Stickler Syndrome, Bardet-Biedl Syndrome, Senior-Loken Syndrome and Joubert Syndrome.

Retinal dystrophies are a broad group of clinically and genetically heterogenous disorders affecting the retina (Reviewed in PMID: 26835369). Common presentations among these disorders include night or colour blindness, tunnel vision and subsequent progression to complete blindness. Vision loss can occur anywhere from early infancy to late adulthood and both stationary and progressive diseases have been described. The inheritance pattern may be autosomal recessive, autosomal dominant or X-linked. Sporadic cases are also observed. Mutations within the same gene have been shown to cause different disease phenotypes, even among affected individuals within the same family highlighting further levels of complexity. Retinal dystrophy can be nonsyndromic or part of a syndrome in which clinical presentations extend to more than the affected retina. Examples of retinal dystrophies associated with syndromic features are Usher syndrome, Bardet-Biedl syndrome, Joubert syndrome, Senior-Loken syndrome, Cohen syndrome and Alström syndrome. For detailed description of different retinal dystrophies, please see the ophthalmology subpanel descriptions.

Genes in the Retinal Dystrophy Panel and their clinical significance

To view complete table content, scroll horizontally.

Gene Associated phenotypes Inheritance ClinVar HGMD
ABCA4 Stargardt disease, Retinitis pigmentosa, Cone rod dystrophy, Retinal dystrophy, early-onset severe, Fundus flavimaculatus AR 308 1231
ABCC6* Pseudoxanthoma elasticum AR 352 377
ABCD1* Adrenoleukodystrophy XL 95 663
ABHD12 Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract AR 16 20
ACO2 Optic atrophy, Infantile cerebellar-retinal degeneration AD/AR 16 15
ADAM9 Cone rod dystrophy AR 6 10
ADAMTS18 Knobloch syndrome 2, Microcornea, myopic chorioretinal atrophy, and telecanthus, Retinal dystrophy, early onset, autosomal recessive AR 4 14
ADGRV1 Usher syndrome, type IIC AR 71 236
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 AR 10 79
ALMS1* Alström syndrome AR 197 302
AMACR Alpha-methylacyl-CoA racemase deficiency, Bile acid synthesis defect AR 3 8
ARHGEF18 Retinitis pigmentosa 78 AR 5 6
ARL13B Joubert syndrome AR 11 10
ARL2BP Retinitis pigmentosa with or without situs inversus AR 4 4
ARL3 Retinitis pigmentosa, Joubert syndrome AD/AR 1
ARL6 Bardet-Biedl syndrome, Retinitis pigmentosa AR 14 21
ARMC9 Joubert syndrome 30 AR 12 11
ARR3 3 3
ARSG Usher syndrome, type IV AR 1 1
ATF6 Achromatopsia AR 13 13
ATOH7 Persistent hyperplastic primary vitreous, autosomal recessive AR 4 9
B9D1 Meckel syndrome AR 7 10
B9D2 Meckel syndrome AR 8 4
BBIP1 Bardet-Biedl syndrome 18 AR 1 1
BBS1 Bardet-Biedl syndrome AR 66 103
BBS10 Bardet-Biedl syndrome AR 90 107
BBS12 Bardet-Biedl syndrome AR 36 58
BBS2 Bardet-Biedl syndrome, Retinitis pigmentosa AR 58 91
BBS4 Bardet-Biedl syndrome AR 25 53
BBS5 Bardet-Biedl syndrome AR 18 31
BBS7 Bardet-Biedl syndrome AR 19 43
BBS9 Bardet-Biedl syndrome AR 27 52
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
C5ORF42 Orofaciodigital syndrome VI, Joubert syndrome 17 AR 97 103
C8ORF37 Retinitis pigmentosa, Cone rod dystrophy, Bardet-Biedl syndrome 21 AR 8 17
CA4 Retinitis pigmentosa 17 AD 3 10
CABP4 Night blindness, congenital stationary AR 6 11
CACNA1F Aland Island eye disease, Cone rod dystrophy, Night blindness, congenital stationary XL 39 182
CACNA2D4 Retinal cone dystrophy AR 3 9
CAPN5 Vitreoretinopathy, neovascular inflammatory AD 3 12
CC2D2A# COACH syndrome, Joubert syndrome, Meckel syndrome AR 76 91
CDH23 Deafness, Usher syndrome, type 1D AR 94 358
CDH3 Hypotrichosis, congenital, with juvenile macular dystrophy, Ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome AR 7 30
CDHR1 Retinitis pigmentosa, Cone rod dystrophy AR 12 48
CEP104 Joubert syndrome AR 7 5
CEP120 Short-rib thoracic dysplasia 13 with or without polydactyly AR 9 9
CEP164 Nephronophthisis AR 11 9
CEP19 Morbid obesity and spermatogenic failure, Bardet-Biedl syndrome AR 2 2
CEP250 Cone rod dystrophy and hearing loss AR 5
CEP290* Bardet-Biedl syndrome, Leber congenital amaurosis, Joubert syndrome, Senior-Loken syndrome, Meckel syndrome AR 130 289
CEP41 Joubert syndrome AR/Digenic 7 11
CEP78 Cone rod dystrophy and hearing loss AR 7 9
CEP83 Nephronophthisis AR 10 10
CERKL Retinitis pigmentosa AR 20 37
CHM# Choroideremia XL 46 284
CIB2 Deafness, Usher syndrome type IJ AR 5 18
CISD2* Wolfram syndrome 2 AR 2 4
CLN3 Neuronal ceroid lipofuscinosis, type 3 AR 100 72
CLN5 Neuronal ceroid lipofuscinosis, type 5 AR 62 47
CLN6 Neuronal ceroid lipofuscinosis, type 6 AR 41 83
CLN8 Neuronal ceroid lipofuscinosis, type 8 AR 45 44
CLRN1 Retinitis pigmentosa, Usher sydnrome, type 3A AR 24 39
CNGA1# Retinitis pigmentosa AR 14 33
CNGA3 Leber congenital amaurosis, Achromatopsia AR 32 149
CNGB1 Retinitis pigmentosa AR 25 61
CNGB3 Macular degeneration, juvenile, Achromatopsia AR 115 124
CNNM4 Jalili syndrome AR 11 24
COL11A1 Marshall syndrome, Fibrochondrogenesis, Stickler syndrome type 2, Deafness AD/AR 34 94
COL11A2 Weissenbacher-Zweymuller syndrome, Deafness, Otospondylomegaepiphyseal dysplasia, Fibrochondrogenesis, Stickler syndrome type 3 (non-ocular) AD/AR 29 57
COL18A1 Knobloch syndrome AR 27 31
COL2A1 Avascular necrosis of femoral head, Rhegmatogenous retinal detachment, Epiphyseal dysplasia, with myopia and deafness, Czech dysplasia, Achondrogenesis type 2, Platyspondylic dysplasia Torrance type, Hypochondrogenesis, Spondyloepiphyseal dysplasia congenital (SEDC), Spondyloepimetaphyseal dysplasia (SEMD) Strudwick type, Kniest dysplasia, Spondyloperipheral dysplasia, Mild SED with premature onset arthrosis, SED with metatarsal shortening, Stickler syndrome type 1 AD 180 561
COL9A1 Multiple epiphyseal dysplasia type 6 (EDM6), Stickler syndrome, type IV AD/AR 9 6
COL9A2 Stickler syndrome, Multiple epiphyseal dysplasia type 2 (EDM2) AD/AR 7 12
COL9A3 Multiple epihyseal dysplasia type 3 (EDM3), Stickler syndrome recessive type AD/AR 10 14
COQ2 Coenzyme Q10 deficiency AR 16 31
CPE Obesity, severe, and type II diabetes AR 2
CRB1 Retinitis pigmentosa, Pigmented paravenous chorioretinal atrophy, Leber congenital amaurosis AR 54 334
CRX Cone rod dystrophy, Leber congenital amaurosis AD/AR 30 106
CSPP1 Jeune asphyxiating thoracic dystrophy, Joubert syndrome AR 32 27
CTC1 Cerebroretinal microangiopathy with calcifications and cysts AR 21 33
CTNNA1 Macular dystrophy, patterned 2 AD 6 10
CTNNB1 Exudative vitreoretinopathy 7, Mental retardation, autosomal dominant 19 AD 90 51
CTSD Ceroid lipofuscinosis, neuronal AR 12 18
CWC27 Retinitis pigmentosa with or without skeletal anomalies (RPSKA) AR 5 7
CYP4V2 Retinitis pigmentosa, Bietti crystalline corneoretinal dystrophy AR 31 94
DFNB31 Usher syndrome, type 2D, Deafness, autosomal recessive 31 AR 12 31
DHDDS Retinitis pigmentosa, Developmental delay and seizures with or without movement abnormalities (DEDSM) AD/AR 5 8
DHX38 Retinitis pigmentosa AR 1
DNAJC5 Kufs disease,, Ceroid lipofuscinosis, neuronal 4, Parry AD 2 2
DRAM2 Cone-rod dystrophy 21 AR 8 10
DTHD1 Leber congenital amaurosis with muscle dystrophy AR 1
DYNC2H1 Short -rib thoracic dysplasia with or without polydactyly type 1, Short -rib thoracic dysplasia with or without polydactyly type 3, Asphyxiating thoracic dysplasia (ATD; Jeune), SRPS type 2 (Majewski) AR/Digenic 148 205
EFEMP1 Doyne honeycomb degeneration of retina, Malattia leventinese AD 2 8
ELOVL4 Stargardt disease, Icthyosis, spastic quadriplegia, and mental retardation, Spinocerebellar ataxia AD/AR 13 14
EMC1 Cerebellar atrophy, visual impairment, and psychomotor retardation AR 3 7
ESPN* Deafness, Deafness, autosomal recessive 36 AD/AR 12 15
EXOSC2 2 2
EYS* Retinitis pigmentosa AR 97 321
FAM161A Retinitis pigmentosa AR 14 20
FDXR Auditory neuropathy and optic atrophy AR 5 19
FLVCR1 Ataxia, posterior column, with retinitis pigmentosa AR 9 15
FRMD7 Nystagmus, infantile periodic alternating XL 15 95
FZD4 Retinopathy of prematurity, Exudative vitreoretinopathy AD/Digenic 14 90
GNAT1 Night blindness, congenital stationary AD/AR 5 10
GNAT2 Achromatopsia AR 7 16
GNB3 Night blindness, congenital stationary, type 1H AR 3 6
GNPTG Mucolipidosis AR 45 46
GPR143 Nystagmus, congenital, Ocular albinism XL 22 181
GPR179 Night blindness, congenital stationary AR 13 16
GRK1 Oguchi disease AR 5 23
GRM6 Night blindness, congenital stationary AR 11 38
GUCA1A Cone dystrophy 3/Cone rod dystrophy AD 7 21
GUCY2D Cone rod dystrophy, Leber congenital amaurosis AD/AR 34 235
HARS Charcot-Marie-Tooth disease, axonal, type 2W, Usher syndrome, type 3B AD/AR 6 12
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
HMX1 Oculoauricular syndrome AR 3 4
IDH3A Leber congenital amaurosis AR 7
IDH3B Retinitis pigmentosa AR 2 3
IFT140 Short -rib thoracic dysplasia with or without polydactyly, Asphyxiating thoracic dysplasia (ATD; Jeune) AR 38 63
IFT172 Retinitis pigmentosa, Short -rib thoracic dysplasia with or without polydactyly, Asphyxiating thoracic dysplasia (ATD; Jeune) AR 22 25
IFT27 Bardet Biedl syndrome 19 AR 1 4
IFT81# Short rib thoracic dysplasia with polydactyly, Cone-Rod dystrophy, autosomal recessive AR 4 9
IMPDH1 Retinitis pigmentosa, Leber congenital amaurosis AD 7 23
IMPG1 Macular dystrophy, vitelliform AD/AR 9 11
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
INVS Nephronophthisis AR 16 34
IQCB1 Senior-Loken syndrome AR 24 41
ISPD Muscular dystrophy-dystroglycanopathy AR 38 53
JAG1 Alagille syndrome AD 131 610
KCNJ13 Snowflake vitreoretinal degeneration, Leber congenital amaurosis AD/AR 6 10
KCNV2 Retinal cone dystrophy AR 16 94
KIAA0556 Joubert syndrome 26 AR 2 2
KIAA0586# Short rib thoracic dysplasia with polydactyly, Joubert syndrome AR 29 31
KIAA0753 Orofaciodigital syndrome XV AR 6 7
KIAA1549 Retinitis pigmentosa AR 1 6
KIF11 Microcephaly, Microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability AD 39 69
KIF7 Acrocallosal syndrome, Hydrolethalus syndrome, Al-Gazali-Bakalinova syndrome, Joubert syndrome AR/Digenic 24 44
KIZ Retinitis pigmentosa 69 AR 3 4
KLHL7 Retinitis pigmentosa, Retinitis pigmentosa 42, Cold-induced sweating syndrome 3 AD/AR 12 11
LAMA1 Poretti-Boltshauser syndrome AR 32 40
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
LRIT3 Night blindness, congenital stationary AR 4 9
LRP2 Donnai-Barrow syndrome, Faciooculoacousticorenal syndrome AR 24 38
LRP5* Van Buchem disease, Osteoporosis-pseudoglioma syndrome, Hyperostosis, endosteal, Osteosclerosis, Exudative vitreoretinopathy, Osteopetrosis late-onset form type 1, LRP5 primary osteoporosis AD/AR/Digenic 57 196
LZTFL1 Bardet-Biedl syndrome 17 AR 6 3
MAK Retinitis pigmentosa AR 11 22
MERTK Retinitis pigmentosa AR 25 75
MFN2 Hereditary motor and sensory neuropathy, Charcot-Marie-Tooth disease AD/AR 70 223
MFRP Microphthalmia, isolated 5, Nanophthalmos 2, Retinitis pigmentosa, autosomal recessive AR 27 30
MFSD8 Ceroid lipofuscinosis, neuronal AR 27 47
MKKS Bardet-Biedl syndrome, McKusick-Kaufman syndrome AR 21 59
MKS1 Bardet-Biedl syndrome, Meckel syndrome AR 50 52
MMACHC Methylmalonic aciduria and homocystinuria AR 59 93
MT-ATP6 Neuropathy, ataxia, and retinitis pigmentosa, Leber hereditary optic neuropathy, Ataxia and polyneuropathy, adult-onset, Cardiomyopathy, infantile hypertrophic, Leigh syndrome, Striatonigral degeneration, infantile, mitochondrial Mitochondrial 19
MT-ATP8 Cardiomyopathy, apical hypertrophic, and neuropathy, Cardiomyopathy, infantile hypertrophic Mitochondrial 4
MT-CO1 Myoglobinuria, recurrent, Leber hereditary optic neuropathy, Sideroblastic anemia, Cytochrome C oxidase deficiency, Deafness, mitochondrial Mitochondrial 17
MT-CO2 Cytochrome c oxidase deficiency Mitochondrial 8
MT-CO3 Cytochrome c oxidase deficiency, Leber hereditary optic neuropathy Mitochondrial 9
MT-CYB Mitochondrial 69
MT-ND1 Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, Leber hereditary optic neuropathy, Leber optic atrophy and dystonia Mitochondrial 21
MT-ND2 Leber hereditary optic neuropathy, Mitochondrial complex I deficiency Mitochondrial 6
MT-ND3 Leber optic atrophy and dystonia, Mitochondrial complex I deficiency Mitochondrial 7
MT-ND4 Leber hereditary optic neuropathy, Leber optic atrophy and dystonia, Mitochondrial complex I deficiency Mitochondrial 11
MT-ND4L Leber hereditary optic neuropathy Mitochondrial 2
MT-ND5 Myoclonic epilepsy with ragged red fibers, Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, Leber hereditary optic neuropathy, Mitochondrial complex I deficiency Mitochondrial 19
MT-ND6 Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, Oncocytoma, Leber hereditary optic neuropathy, Leber optic atrophy and dystonia, Mitochondrial complex I deficiency Mitochondrial 16
MT-RNR1 Deafness, mitochondrial Mitochondrial 3
MT-RNR2 Chloramphenicol toxicity/resistance Mitochondrial 2
MT-TA Mitochondrial 4
MT-TC Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes Mitochondrial 3
MT-TD Mitochondrial 1
MT-TE Diabetes-deafness syndrome, Mitochondrial myopathy, infantile, transient, Mitochondrial myopathy with diabetes Mitochondrial 5
MT-TF Myoclonic epilepsy with ragged red fibers, Nephropathy, tubulointerstitial, Encephalopathy, mitochondrial, Epilepsy, mitochondrial, Myopathy, mitochondrial, Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes Mitochondrial 7
MT-TG Mitochondrial 3
MT-TH Mitochondrial 4
MT-TI Mitochondrial 7
MT-TK Myoclonic epilepsy with ragged red fibers, Leigh syndrome Mitochondrial 5
MT-TL1 Cytochrome c oxidase deficiency, Myoclonic epilepsy with ragged red fibers, Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, Diabetes-deafness syndrome, Cyclic vomiting syndrome, SIDS, susceptibility to Mitochondrial 14
MT-TL2 Mitochondrial multisystemic disorder, Progressive external ophthalmoplegia, Mitochondrial Myopathy, Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes Mitochondrial 5
MT-TM Leigh syndrome, Mitochondrial multisystemic disorder Mitochondrial 1
MT-TN Progressive external ophthalmoplegia, Mitochondrial multisystemic disorder Mitochondrial 3
MT-TP Mitochondrial 2
MT-TQ Mitochondrial multisystemic disorder Mitochondrial 2
MT-TR Encephalopathy, mitochondrial Mitochondrial 2
MT-TS1 Myoclonic epilepsy with ragged red fibers, Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes Mitochondrial 10
MT-TS2 Mitochondrial multisystemic disorder Mitochondrial 2
MT-TT Mitochondrial 5
MT-TV Hypertrophic cardiomyopathy (HCM), Leigh syndrome, Mitochondrial multisystemic disorder, Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes Mitochondrial 3
MT-TW Leigh syndrome, Myopathy, mitochondrial Mitochondrial 8
MT-TY Mitochondrial multisystemic disorder Mitochondrial 4
MTTP Abetalipoproteinemia AR 12 69
MVK Mevalonic aciduria, Hyper-IgD syndrome, Porokeratosis 3, multiple types AD/AR 35 181
MYO7A Deafness, autosomal dominant 11, Usher syndrome, type I, Deafness, autosomal recessive 2 AD/AR 239 515
NAGLU Mucopolysaccharidosis (Sanfilippo syndrome), Charcot-Marie-Tooth disease, axonal, type 2V AR 74 171
NDP Exudative vitreoretinopathy, Norrie disease XL 31 167
NEK2# Retinitis pigmentosa 67 AR 1 1
NMNAT1# Leber congenital amaurosis AR 20 74
NPHP1 Nephronophthisis, Joubert syndrome, Senior-Loken syndrome AR 19 76
NPHP3 Nephronophthisis, Renal-hepatic-pancreatic dysplasia, Meckel syndrome AR 38 75
NPHP4 Nephronophthisis, Senior-Loken syndrome AR 20 113
NR2E3 Retinitis pigmentosa, Enhanced S-cone syndrome AD/AR 19 77
NR2F1 Bosch-Boonstra optic atrophy syndrome AD 23 34
NRL Retinitis pigmentosa, Clumped pigmentary retinal degeneration AD/AR 11 25
NYX Night blindness, congenital stationary XL 12 89
OAT Gyrate atrophy of choroid and retina AR 67 71
OCA2 Albinism, brown oculocutaneous, Albinism, oculocutaneous, Skin/hair/eye pigmentation AR 43 310
OFD1 Simpson-Golabi-Behmel syndrome, Retinitis pigmentosa, Orofaciodigital syndrome, Joubert syndrome XL 153 160
OPA1 Optic atrophy, Optic atrophy 1, Optic atrophy with or without deafness, Ophthalmoplegia, myopathy, ataxia, and neuropathy, Behr synrome, Mitochondrial DNA depletion syndrome 14 AD/AR 96 390
OPA3 Optic atrophy, 3-methylglutaconic aciduria AD/AR 13 15
OPN1SW Tritanopia AD 3 9
OTX2 Microphthalmia, syndromic, Pituitary hormone deficiency, combined, Retinal dystrophy, early-onset, and pituitary dysfunction AD 23 73
P3H2 Myopia, high, with cataract and vitreoretinal degeneration AR 7 7
PANK2 Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration, Neurodegeneration with brain iron accumulation AR 37 181
PAX2 Isolated renal hypoplasia, Papillorenal syndrome, Focal segmental glomerulosclerosis 7 AD 30 96
PCDH15 Deafness, Usher syndrome, type 1D AR/Digenic 113 118
PCYT1A Spondylometaphyseal dysplasia with cone-rod dystrophy AR 12 20
PDE6A Retinitis pigmentosa AR 16 49
PDE6B Retinitis pigmentosa, Night blindness, congenital stationary AD/AR 35 125
PDE6C Cone dystrophy AR 31 44
PDE6D Joubert syndrome 22 AR 3 1
PDE6G Retinitis pigmentosa AR 1 2
PDE6H Retinal cone dystrophy, Achromatopsia AR 2 2
PDSS1# Coenzyme Q10 deficiency AR 5 3
PDSS2 Coenzyme Q10 deficiency AR 8 4
PDZD7# Deafness, autosomal recessive AR 11 19
PEX1 Heimler syndrome, Peroxisome biogenesis factor disorder 1A, Peroxisome biogenesis factor disorder 1B AR 112 134
PEX10 Adrenoleukodystrophy, neonatal, Zellweger syndrome, Peroxisome biogenesis disorder, Ataxia AR 34 29
PEX11B Zellweger syndrome, Peroxisome biogenesis disorder AR 5 7
PEX12 Zellweger syndrome, Peroxisome biogenesis disorder AR 43 37
PEX13 Adrenoleukodystrophy, neonatal, Zellweger syndrome, Peroxisome biogenesis disorder AR 9 10
PEX14 Peroxisome biogenesis factor disorder 14, Zellweger syndrome AR 5 4
PEX16 Zellweger syndrome, Peroxisome biogenesis disorder AR 8 13
PEX19 Peroxisome biogenesis disorder, 19, Zellweger syndrome AR 3 4
PEX2 Zellweger syndrome, Peroxisome biogenesis disorder AR 16 18
PEX26 Adrenoleukodystrophy, neonatal, Zellweger syndrome, Peroxisome biogenesis disorder AR 13 27
PEX3 Zellweger syndrome, Peroxisome biogenesis disorder AR 4 10
PEX5 Adrenoleukodystrophy, neonatal, Rhizomelic chondrodysplasia punctata, Zellweger syndrome, Peroxisome biogenesis disorder AR 8 14
PEX6 Heimler syndrome, Peroxisome biogenesis disorder 4A, Peroxisome biogenesis disorder 4B AR 58 107
PEX7 Refsum disease, Rhizomelic CDP type 1 AR 44 53
PHYH Refsum disease AR 12 36
PISD AR
PITPNM3 Cone-rod dystrophy 5 AD 1 5
PLA2G5 Fleck retina, familial benign AR 1 7
PLK4 Microcephaly and chorioretinopathy, autosomal recessive 2 AR 3 6
PNPLA6 Laurence-Moon syndrome, Boucher-Neuhauser syndrome, Spastic paraplegia 39 AR 26 58
POC1B Cone-rod dystrophy 20 AR 4 7
POMGNT1 Muscular dystrophy-dystroglycanopathy AR 96 88
PPT1 Ceroid lipofuscinosis, neuronal AR 94 77
PRCD Retinitis pigmentosa AR 2 7
PRDM13 Macular dystrophy, retinal 1, North Carolina type AD/AR 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
PRPS1* Phosphoribosylpyrophosphate synthetase I superactivity, Arts syndrome, Charcot-Marie-Tooth disease, X-linked recessive, 5, Deafness, X-linked 1 XL 27 32
RAB28 Cone-rod dystrophy 18 AR 4 5
RAX2 Cone rod dystrophy AD/AR 5 4
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 AR 6 9
RD3 Leber congenital amaurosis AR 5 13
RDH11 Microphthalmia, isolated, with coloboma 10, Retinal dystrophy, juvenile cataracts, and short stature syndrome AR 2 2
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
RGS9 Bradyopsia AR 2 2
RGS9BP Bradyopsia AR 2 7
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 AD/AR 3 18
RP1 Retinitis pigmentosa AD/AR 45 181
RP1L1 Occult macular dystrophy, Retinitis pigmentosa AD/AR 7 48
RP2 Retinitis pigmentosa XL 26 118
RPE65 Retinitis pigmentosa, Leber congenital amaurosis AD/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
RPGRIP1L# COACH syndrome, Joubert syndrome, Meckel syndrome, Retinal degeneration in ciliopathy, modifier AR 39 49
RS1 Retinoschisis XL 44 262
RTN4IP1 Optic atrophy 10 with or without ataxia, mental retardation, and seizures AR 2 12
SAG Retinitis pigmentosa, Oguchi disease AD/AR 6 15
SAMD11 Retinitis pigmentosa AR 2 5
SCAPER Retinal dystrophy, Retinitis pigmentosa AR 4 7
SCLT1# Senior-Loken syndrome, Retinal dystrophy AR 3
SDCCAG8 Bardet-Biedl syndrome, Senior-Loken syndrome AR 14 18
SEMA4A Retinitis pigmentosa, Cone rod dystrophy AR 4 14
SGSH Mucopolysaccharidosis (Sanfilippo syndrome) AR 55 148
SLC24A1 Night blindness, congenital stationary, type 1D AR 7 26
SLC25A46 Neuropathy, hereditary motor and sensory, type VIB AR 14 17
SLC45A2 Skin/hair/eye pigmentation, Oculocutaneous albinism AR 16 156
SLC7A14 Retinitis pigmentosa 68 AR 4 8
SNRNP200 Retinitis pigmentosa AD/AR 6 34
SPATA7 Leber congenital amaurosis, Retitinitis pigmentosa AR 15 39
SPP2 Retinitis pigmentosa AD 1 2
SRD5A3* Kahrizi syndrome, Congenital disorder of glycosylation, Retinal dystrophy AR 13 16
TCTN1# Joubert syndrome AR 6 6
TCTN2 Joubert syndrome, Meckel syndrome AR 20 15
TCTN3 Orofaciodigital syndrome (Mohr-Majewski syndrome), Joubert syndrome AR 9 12
TEAD1 Sveinsson choreoretinal atrophy AD 1 2
TIMM8A* Mohr-Tranebjaerg syndrome, Jensen syndrome, Opticoacoustic nerve atrophy with dementia XL 11 21
TIMP3 Sorsby fundus dystrophy AD 6 17
TMEM107 Joubert syndrome AR 10 3
TMEM126A Optic atrophy AR 3 1
TMEM138 Joubert syndrome AR 6 8
TMEM216 Joubert syndrome, Meckel syndrome AR 17 8
TMEM231 Joubert syndrome, Meckel syndrome AR 12 19
TMEM237 Joubert syndrome AR 7 11
TMEM67 Nephronophthisis, COACH syndrome, Joubert syndrome, Meckel syndrome AR 87 170
TOPORS Retinitis pigmentosa AD 7 22
TPP1 Spinocerebellar ataxia, Neuronal ceroid lipofuscinosis type 2 AR 75 112
TRAF3IP1 Senior-Loken syndrome 9 AR 11 15
TREX1 Vasculopathy, retinal, with cerebral leukodystrophy, Chilblain lupus, Aicardi-Goutières syndrome AD/AR 30 71
TRIM32 Bardet-Biedl syndrome, Muscular dystrophy, limb-girdle AR 13 16
TRPM1 Night blindness, congenital stationary AR 21 82
TSPAN12 Exudative vitreoretinopathy, Retinal dysplasia and severe familial exudative vitreoretinopathy AD/AR 16 51
TTC21B Short-rib thoracic dysplasia, Nephronophthisis, Asphyxiating thoracic dysplasia (ATD; Jeune) AR 23 63
TTC8 Bardet-Biedl syndrome, Retinitis pigmentosa AR 5 16
TTLL5 Cone-rod dystrophy 19 AR 13 12
TTPA Ataxia with isolated vitamin E deficiency AR 29 30
TUB Retinal dystrophy and obesity AR 1 2
TUBB4B Leber congenital amaurosis, Hearing loss AD 2 3
TUBGCP4 Microcephaly and chorioretinopathy, autosomal recessive 3 AR 7 6
TUBGCP6 Microcephaly and chorioretinopathy, autosomal recessive 1 AR 16 7
TULP1 Retinitis pigmentosa, Leber congenital amaurosis AR 24 74
TYR* Albinism, oculocutaneous AR 77 441
TYRP1 Albinism, oculocutaneous AR 10 55
USH1C Deafness, Usher syndrome, type IC AR 45 51
USH1G Usher syndrome, type 1G AR 13 32
USH2A Retinitis pigmentosa 39, Usher syndrome, type 2A AR 401 1169
VCAN Wagner disease AD 11 19
VPS13B Cohen syndrome AR 351 203
WDPCP Meckel-Gruber syndrome, modifier, Bardet-Biedl syndrome, Congenital heart defects, hamartomas of tongue, and polysyndactyly AR 6 8
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
WFS1 Wolfram syndrome, Wolfram-like syndrome, autosomal dominant, Deafness, autosomal dominant 6/14/38, Cataract 41 AD/AR 69 362
YME1L1* Optic atrophy 11 1 1
ZNF408 Exudative vitreoretinopathy 6, Retinitis pigmentosa 72 AD/AR 3 9
ZNF423 Nephronophthisis, Joubert syndrome AD/AR 10 7
ZNF513 Retinitis pigmentosa AR 1 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 Retinal Dystrophy Panel

To view complete table content, scroll horizontally.

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
ABCC6 Chr16:16244424 c.4403+11C>G NM_001171.5 rs72664215
ABCC6 Chr16:16256835 c.3506+15G>A NM_001171.5 rs72664302
ABCC6 Chr16:16281097 c.1780-29T>A NM_001171.5 rs72664206
ABCC6 Chr16:16284246 c.1432-22C>A NM_001171.5 rs72664297
BBS1 Chr11:66291105 c.951+58C>T NM_024649.4
BBS4 Chr15:73001820 c.77-216delA NM_033028.4 rs113994189
BBS5 Chr2:170354110 c.619-27T>G NM_152384.2
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
CLN6 Chr15:68506515 c.297+113G>C NM_017882.2
CLRN1 Chr3:150660197 c.254-649T>G NM_001195794.1 rs976853535
CNGA3 Chr2:98986401 c.-37-1G>C NM_001298.2
COL11A1 Chr1:103386637 c.3744+437T>G NM_080629.2
COL11A1 Chr1:103488576 c.1027-24A>G NM_080629.2
COL11A1 Chr1:103491958 c.781-450T>G NM_080629.2 rs587782990
COL2A1 Chr12:48379984 c.1527+135G>A NM_001844.4
DHDDS Chr1:26774026 c.441-24A>G NM_024887.3 rs764831063
DYNC2H1 Chr11:103019205 c.2819-14A>G NM_001080463.1 rs781091611
DYNC2H1 Chr11:103055609 c.6478-16G>A NM_001080463.1 rs376892534
EYS Chr6:66417023 c.-448+5G>A NM_001142800.1
FRMD7 ChrX:131228285 c.285-118C>T NM_194277.2
GNAT2 Chr1:110151229 c.461+24G>A NM_005272.3 rs397515384
GNPTG Chr16:1412562 c.610-16_609+28del NM_032520.4 rs193302853
GPR143 ChrX:9708630 c.885+748G>A NM_000273.2
GPR143 ChrX:9711844 c.659-131T>G NM_000273.2
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
JAG1 Chr20:10629767 c.1349-12T>G NM_000214.2
LRAT Chr4:155670121 c.541-15T>G NM_004744.3 rs779487944
MTTP Chr4:100512792 c.619-5_619-2delTTTA NM_000253.2 rs755155385
MTTP Chr4:100522736 c.1237-28A>G NM_000253.2
MVK Chr12:110029032 c.769-7dupT NM_000431.2 rs104895348
MYO7A Chr11:76839534 c.-48A>G NM_000260.3
MYO7A Chr11:76893448 c.3109-21G>A NM_000260.3
MYO7A Chr11:76915107 c.5327-14T>G NM_000260.3
MYO7A Chr11:76915110 c.5327-11A>G NM_000260.3 rs397516316
MYO7A Chr11:76919448 c.5857-27_5857-26insTTGAG NM_000260.3
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
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
OCA2 Chr15:28234823 c.1117-11T>A NM_000275.2
OCA2 Chr15:28234829 c.1117-17T>C NM_000275.2 rs200081580
OCA2 Chr15:28235808 c.1045-15T>G NM_000275.2 rs779461179
OCA2 Chr15:28267738 c.574-19A>G NM_000275.2 rs145242923
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
OPA1 Chr3:193334932 c.449-34dupA NM_130837.2
OPA1 Chr3:193374829 c.2179-40G>C NM_130837.2
PANK2 Chr20:3903981 c.*40G>C NM_153638.2
PCDH15 Chr10:56560684 c.-29+1G>C NM_001142763.1
PDE6C Chr10:95380377 c.481-12T>A NM_006204.3 rs786200909
PEX6 Chr6:42933858 c.2301-15C>G NM_000287.3 rs267608236
PEX6 Chr6:42933952 c.2300+28G>A NM_000287.3 rs267608237
PEX7 Chr6:137143759 c.-45C>T NM_000288.3 rs267608252
PPT1 Chr1:40539203 c.*526_*529delATCA NM_000310.3 rs386833624
PPT1 Chr1:40558194 c.125-15T>G NM_000310.3 rs386833629
PRDM13 Chr6:100040906 c.-14005G>T .
PRDM13 Chr6:100040987 c.-13924G>C .
PRDM13 Chr6:100041040 c.-13871C>T .
PRDM13 Chr6:100046783 c.-8128A>C NM_021620.3
PRDM13 Chr6:100046804 c.-8107T>C NM_021620.3
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 Chr14:21793564 c.2367+23delG NM_020366.3
RPGRIP1 Chr14:21795769 c.2711-13G>T NM_020366.3 rs369991630
SGSH Chr17:78190802 c.249+27_249+28delGG NM_000199.3
SLC45A2 Chr5:33985176 NM_016180.3 rs984225803
SLC45A2 Chr5:33985764 NM_016180.3 rs199972025
TIMM8A ChrX:100601671 c.133-23A>C NM_004085.3 rs869320666
TMEM231 Chr16:75575364 c.824-11T>C NM_001077416.2
TPP1 Chr11:6637752 c.887-18A>G NM_000391.3
TYR Chr11:88960973 c.1037-18T>G NM_000372.4
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
WFS1 Chr4:6271704 c.-43G>T NM_006005.3

Test Strengths

The majority of the X-linked RP is caused by mutations in the*RPGR* 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
  • 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

The following exons are not included in the panel as they are not sufficiently covered with high quality sequence reads: *CC2D2A* (NM_020785:7), *CHM* (NM_001145414:5), *CNGA1* (NM_001142564:2), *HK1* (NM_001322365:5), *IFT81* (NM_031473:12), *KIAA0586* (NM_001244189:6, 33), *NEK2* (NM_001204182:8), *NMNAT1* (NM_001297779:5), *PDSS1* (NM_014317:2), *PDZD7* (NM_024895:10), *RPGRIP1L* (NM_015272:23), *SCLT1* (NM_001300898:6), *TCTN1* (NM_001173976:2;NM_024549:6). 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
  • 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 %
ANALYTIC VALIDATION (NA samples; n=4)
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%
CLINICAL VALIDATION (n=76 samples)
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.

Other

Recommendations on Clinical Assessment of Patients with Inherited Retinal Degenerations – 2016

Content last modified: 13 November 2023