- Is a 322 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.
- PLUS
4 weeks
322
OP0801
Large
Summary
The Blueprint Genetics Retinal Dystrophy Panel (test code OP0801):
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 Retinal Dystrophy Panel
ICD-10 | Disease |
---|---|
F84.2 | Rett syndrome |
Q87.89 | Bardet-Biedl syndrome |
Q04.3 | Joubert syndrome |
H35.50 | Usher syndrome, type IV |
Q89.8 | Stickler syndrome |
H35.50 | Norrie disease |
H35.50 | Stargardt disease |
Q14.1 | X-linked retinoschisis |
Q87.89 | Cohen syndrome |
H35.50 | Leber congenital amaurosis |
H49.40 | Progressive external ophthalmoplegia |
H35.50 | Retinal dystrophy |
H35.50 | Cone rod dystrophy |
H53.60 | Congenital stationary night blindness |
H53.51 | Achromatopsia |
H35.50 | Fundus albipunctatus |
Q61.5 | Senior-Loken syndrome |
G60.1 | Refsum disease |
H35.50 | Retinitis pigmentosa |
H31.21 | Choroideremia |
E72.4 | Gyrate atrophy of choroid and retina |
H35.029 | Familial exudative vitreoretinopathy |
G11.9 | Hereditary ataxia |
C94.2 | Acute Megakaryoblastic Leukemia |
K59.8 | Chronic Intestinal Pseudoobstruction |
T36.5 | Adverse effect of aminoglycosides |
G93.41 | Metabolic Encephalopathy |
H49.81 | Kearns Sayre Syndrome |
E88.42 | MERFF Syndrome |
H47.013 | Nonarteritic Anterior Ischemic Optic Neuropathy |
G60.2 | Neuropathy in association with hereditary ataxia |
G30 | Alzheimer's Disease |
G25.5 | Chorea |
G40 | Epilepsy and recurrent seizures |
I42 | Cardiomyopathy |
N26.9 | Focal Segmental Glomerulosclerosis |
G31.82 | Leigh's Disease |
H47.2 | Leber's hereditary optic neuropathy |
G71.3 | Mitochondrial Myopathy |
I42.1 | Hypertrophic Cardiomyopathy |
E11.9 | Non-Insulin Dependent Diabetes Mellitus |
Z86.74 | Personal history of sudden cardiac arrest |
H90.3 | Sensorineural Hearing Loss |
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
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 |
ABHD12 | Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract | AR | 16 | 20 |
ACO2 | Optic atrophy, Infantile cerebellar-retinal degeneration | 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 | Febrile seizures, familial, 4, 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 |
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 |
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, Joubert syndrome | 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 |
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 |
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 | 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 | Stickler syndrome recessive type, Multiple epiphyseal dysplasia type 6 (EDM6) | 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 |
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 |
CWC27 | Retinitis pigmentosa with or without skeletal anomalies (RPSKA) | AR | 5 | 7 |
CYP4V2 | Retinitis pigmentosa, Bietti crystalline corneoretinal dystrophy | AR | 31 | 94 |
DFNB31 | Deafness, Usher syndrome, type 2D | 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 | |
DRAM2 | Cone-rod dystrophy 21 | AR | 8 | 10 |
DTHD1 | Leber congenital amaurosis with muscle dystrophy | AR | 1 | |
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 | AD/AR | 12 | 15 |
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 |
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 | 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 |
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 | 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 |
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 | 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 | 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 | 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 | 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, Deafness, autosomal dominant 11, Usher syndrome, type I | AD/AR | 239 | 515 |
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 |
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 |
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 |
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 |
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 |
PRCD | Retinitis pigmentosa | AR | 2 | 7 |
PRDM13 | Macular dystrophy, retinal 1, North Carolina type | AD | 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 | 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, Intellectual disability, Bardet-Biedl syndrome | AR | 4 | 7 |
SCLT1# | Senior-Loken syndrome, Retinal dystrophy | 3 | ||
SDCCAG8 | Bardet-Biedl syndrome, Senior-Loken syndrome | AR | 14 | 18 |
SEMA4A | Retinitis pigmentosa, Cone rod dystrophy | AR | 4 | 14 |
SLC24A1 | Night blindness, congenital stationary, type 1D | AR | 7 | 26 |
SLC25A46 | Neuropathy, hereditary motor and sensory, type VIB | AR | 14 | 17 |
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 |
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 |
TULP1 | Retinitis pigmentosa, Leber congenital amaurosis | AR | 24 | 74 |
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, Deafness, 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 |
* 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), 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
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 |
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 |
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 |
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 | |
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 |
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 |
TIMM8A | ChrX:100601671 | c.133-23A>C | NM_004085.3 | rs869320666 |
TMEM231 | Chr16:75575364 | c.824-11T>C | NM_001077416.2 | |
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 |
Added and removed genes from the panel
Genes added | Genes removed |
---|---|
MT-ATP6 MT-ATP8 MT-CO1 MT-CO2 MT-CO3 MT-CYB MT-ND1 MT-ND2 MT-ND3 MT-ND4 MT-ND4L MT-ND5 MT-ND6 MT-RNR1 MT-RNR2 MT-TA MT-TC MT-TD MT-TE MT-TF MT-TG MT-TH MT-TI MT-TK MT-TL1 MT-TL2 MT-TM MT-TN MT-TP MT-TQ MT-TR MT-TS1 MT-TS2 MT-TT MT-TV MT-TW MT-TY |
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.
- CAP accredited laboratory
- CLIA-certified personnel performing clinical testing in a CLIA-certified laboratory
- Powerful sequencing technologies, advanced target enrichment methods and precision bioinformatics pipelines ensure superior analytical performance
- Careful construction of clinically effective and scientifically justified gene panels
- Some of the panels include the whole mitochondrial genome (please see the Panel Content section)
- Our Nucleus online portal providing transparent and easy access to quality and performance data at the patient level
- Our publicly available analytic validation demonstrating complete details of test performance
- ~2,000 non-coding disease causing variants in our clinical grade NGS assay for panels (please see ‘Non-coding disease causing variants covered by this panel’ in the Panel Content section)
- Our rigorous variant classification scheme
- Our systematic clinical interpretation workflow using proprietary software enabling accurate and traceable processing of NGS data
- Our comprehensive clinical statements
Test Limitations
The following exons are not included in the panel as they are not sufficiently covered with high quality sequence reads: 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), 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).
- 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).
- Low level mosaicism in nuclear genes (variant with a minor allele fraction of 14.6% is detected with 90% probability)
- Stretches of mononucleotide repeats
- Low level heteroplasmy in mtDNA (>90% are detected at 5% level)
- Indels larger than 50bp
- Single exon deletions or duplications
- Variants within pseudogene regions/duplicated segments
- Some disease causing variants present in mtDNA are not detectable from blood, thus post-mitotic tissue such as skeletal muscle may be required for establishing molecular diagnosis.
The sensitivity of this test may be reduced if DNA is extracted by a laboratory other than Blueprint Genetics.
For additional information, please refer to the Test performance section and see our Analytic Validation.
The genes on the panel have been carefully selected based on scientific literature, mutation databases and our experience.
Our panels are sectioned from our high-quality, clinical grade NGS assay. Please see our sequencing and detection performance table for details regarding our ability to detect different types of alterations (Table).
Assays have been validated for various sample types including EDTA-blood, isolated DNA (excluding from formalin fixed paraffin embedded tissue), saliva and dry blood spots (filter cards). These sample types were selected in order to maximize the likelihood for high-quality DNA yield. The diagnostic yield varies depending on the assay used, referring healthcare professional, hospital and country. Plus analysis increases the likelihood of finding a genetic diagnosis for your patient, as large deletions and duplications cannot be detected using sequence analysis alone. Blueprint Genetics’ Plus Analysis is a combination of both sequencing and deletion/duplication (copy number variant (CNV)) analysis.
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 |
Bioinformatics
The target region for each gene includes coding exons and ±20 base pairs from the exon-intron boundary. In addition, the panel includes non-coding and regulatory variants if listed above (Non-coding variants covered by the panel). Some regions of the gene(s) may be removed from the panel if specifically mentioned in the ‘Test limitations” section above. If the test includes the mitochondrial genome the target region gene list contains the mitochondrial genes. The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. Our pipeline is streamlined to maximize sensitivity without sacrificing specificity. We have incorporated a number of reference population databases and mutation databases including, but not limited, to 1000 Genomes Project, gnomAD, ClinVar and HGMD into our clinical interpretation software to make the process effective and efficient. For missense variants, in silico variant prediction tools such as SIFT, PolyPhen, MutationTaster are used to assist with variant classification. Through our online ordering and statement reporting system, Nucleus, ordering providers have access to the details of the analysis, including patient specific sequencing metrics, a gene level coverage plot and a list of regions with suboptimal coverage (<20X for nuclear genes and <1000X for mtDNA) if applicable. This reflects our mission to build fully transparent diagnostics where ordering providers can easily visualize the crucial details of the analysis process.
Clinical interpretation
We provide customers with the most comprehensive clinical report available on the market. Clinical interpretation requires a fundamental understanding of clinical genetics and genetic principles. At Blueprint Genetics, our PhD molecular geneticists, medical geneticists and clinical consultants prepare the clinical statement together by evaluating the identified variants in the context of the phenotypic information provided in the requisition form. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals regardless of whether they have formal training in genetics.
Variant classification is the corner stone of clinical interpretation and resulting patient management decisions. Our classifications follow the ACMG guideline 2015.
The final step in the analysis is orthogonal confirmation. Sequence and copy number variants classified as pathogenic, likely pathogenic and variants of uncertain significance (VUS) are confirmed using bi-directional Sanger sequencing by orthogonal methods such as qPCR/ddPCR when they do not meet our stringent NGS quality metrics for a true positive call.
Our clinical statement includes tables for sequencing and copy number variants that include basic variant information (genomic coordinates, HGVS nomenclature, zygosity, allele frequencies, in silico predictions, OMIM phenotypes and classification of the variant). In addition, the statement includes detailed descriptions of the variant, gene and phenotype(s) including the role of the specific gene in human disease, the mutation profile, information about the gene’s variation in population cohorts and detailed information about related phenotypes. We also provide links to the references, abstracts and variant databases used to help ordering providers further evaluate the reported findings if desired. The conclusion summarizes all of the existing information and provides our rationale for the classification of the variant.
Identification of pathogenic or likely pathogenic variants in dominant disorders or their combinations in different alleles in recessive disorders are considered molecular confirmation of the clinical diagnosis. In these cases, family member testing can be used for risk stratification. We do not recommend using variants of uncertain significance (VUS) for family member risk stratification or patient management. Genetic counseling is recommended.
Our interpretation team analyzes millions of variants from thousands of individuals with rare diseases. Our internal database and our understanding of variants and related phenotypes increases with every case analyzed. Our laboratory is therefore well-positioned to re-classify previously reported variants as new information becomes available. If a variant previously reported by Blueprint Genetics is re-classified, our laboratory will issue a follow-up statement to the original ordering health care provider at no additional cost.
Other
- American Academy of Ophthalmology. Guideline. 2016. Recommendations of Clinical Assessment of Patients with Inherited Retinal Degeneration - 2016.
- Cohen Syndrome Association
- European Leukodystrophies Association
- Fighting Blindness - Cone Rod Dystrophies
- Fighting Blindness - Stargardts Disease
- Foundation Fighting Blindness - Retinitis Pigmentosa
- Foundation Fighting Blindness - Stargardt Disease
- GARD - CSNB
- GeneReviews - Bardet-Biedl Syndrome
- GeneReviews - Congenital Stationary Night Blindness
- GeneReviews - Familial Exudative Vitreoretinopathy
- GeneReviews - Stickler Syndrome
- GeneReviews - Usher Syndrome Type II
- GeneReviews - X-linked Retinoschisis
- GeneReviews - X-linked retinoschisis
- Joubert Syndrome & Related Disorders Foundation
- NORD - Bardet-Biedl Syndrome
- NORD - Refsum Disease
- NORD - Retinitis Pigmentosa
- NORD - Senior-Loken Syndrome
- NORD - Usher Syndrome
- NORD - X-linked retinoschisis
- Norrie Disease Association
- Patient information UK
- RetNet - Retinal Information Network
- Royal National Institute of Blind People - Retinitis Pigmentosa
- Stone EM et al. 2017. Clinically Focused Molecular Investigation of 1000 Consecutive Families with Inherited Retinal Disease. Ophthalmology. 2017 Sep;124(9):1314-1331.
- The Vision Institut
- The Vision Institut - FEVR
- Usher Syndrome Coalition