Hearing Loss and Deafness, Comprehensive Genetic Testing - Targeted NGS Gene Panel (Hearing Loss and Deafness). Genes: ABHD12, ABHD5, ACOX1, ACTB, ACTG1, ADCY1, ADGRV1, AIFM1, ALMS1, AMMECR1, ANKH, ANLN, ARSG, ATP2B2, ATP6V0A4, ATP6V1B1, ATP6V1B2, BCS1L, BDP1, BSND, BTD, C10ORF2, CABP2, CACNA1D, CATSPER2, CCDC50, - Diagnostic Tests

The Comprehensive Genetic Test for Hearing Loss and Deafness utilizes next-generation sequencing (NGS) to examine 288 genes associated with hearing, inner-ear function, and genetic syndromes that cause hearing loss. It is a targeted gene panel specifically designed to support accurate diagnosis, risk assessment, and prevention.

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The Comprehensive Genetic Test for Hearing Loss and Deafness is an advanced diagnostic test designed to detect mutations across a broad spectrum of genes associated with hereditary hearing loss. Hearing impairment is one of the most common sensory disorders worldwide, with more than half of congenital cases attributed to genetic causes. The comprehensive genetic test for hearing loss and deafness is designed to evaluate both syndromic and non-syndromic forms of hearing loss, whether present at birth or acquired later in life, and to provide an inclusive approach to molecular diagnosis for patients of all ages with sensorineural, conductive, or mixed hearing deficits.

The comprehensive genetic test for hearing loss and deafness includes analyses of more than 100 genes involved in cochlear function, inner ear development, ion transport, hair cell structure, and auditory signaling. Key genes examined include GJB2, GJB6, SLC26A4, TECTA, MYO7A, OTOF, CDH23, TMC1, COL11A2, and STRC. Mutations in these genes can disrupt the normal development and function of the auditory system, resulting in variable degrees of hearing impairment, ranging from mild loss to profound congenital deafness. Many of these mutations follow autosomal recessive or autosomal dominant inheritance patterns, though mitochondrial and X-linked forms are also included in the panel.

Syndromic forms of hearing loss, in which hearing impairment occurs as part of a broader condition, can also be identified by this panel. Genes linked to syndromes such as Usher syndrome (MYO7A, USH2A), Pendred syndrome (SLC26A4), Waardenburg syndrome (MITF, PAX3), and Jervell and Lange-Nielsen syndrome (KCNE1, KCNQ1) are included. This enables simultaneous detection of hearing-related symptoms and associated systemic manifestations affecting vision, pigmentation, cardiac function, and vestibular balance.

Early identification of the genetic causes of hearing loss provides critical insights into expected progression, potential reversibility, and optimal therapeutic approaches, including cochlear implants, hearing aids, and targeted gene therapies currently in development. The comprehensive genetic test for hearing loss and deafness is particularly valuable for newborns who fail hearing screening tests, children with delayed language development, individuals with bilateral or asymmetric hearing loss, and families with a history of hearing impairment.

By pinpointing the molecular origin of hearing loss, The comprehensive genetic test for hearing loss and deafness enables precise classification, informs prognosis, supports family planning through carrier screening and prenatal diagnosis, and contributes to long-term auditory and developmental care through a precision medicine framework.

The test is performed in a clinical laboratory accredited to ISO 15189 and certified by CLIA and CAP, ensuring the validity, accuracy and international recognition of the results.

Genes and Associated Phenotypes (Comprehensive Hearing Loss and Deafness Panel)

Gene	Associated phenotypes	Inheritance	ClinVar	HGMD
ABHD12	Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract	AR	16	20
ABHD5	Chanarin-Dorfman syndrome	AR	11	39
ACOX1	Peroxisomal acyl-CoA oxidase deficiency	AD/AR	15	26
ACTB*	Baraitser-Winter syndrome	AD	55	60
ACTG1*	Deafness, Baraitser-Winter syndrome	AD	27	47
ADCY1	Deafness	AR	1	1
ADGRV1	Usher syndrome, type IIC	AR	71	236
AIFM1	Deafness, Combined oxidative phosphorylation deficiency 6, Cowchock syndrome	XL	27	31
ALMS1*	Alström syndrome	AR	197	302
AMMECR1	Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis	XL	4	5
ANKH	Calcium pyrophosphate deposition disease (familial chondrocalcinosis type 2), Craniometaphyseal dysplasia autosomal dominant type	AD	13	20
ANLN	Focal segmental glomerulosclerosis	AD	2	4
ARSG	Usher syndrome, type IV	AR	1	1
ATP2B2	Sensorineural hearing loss	AD	3	7
ATP6V0A4	Renal tubular acidosis, distal	AR	16	84
ATP6V1B1	Renal tubular acidosis with deafness	AR	15	56
ATP6V1B2	Deafness, congenital, with onychodystrophy, autosomal dominant, Zimmermann-Laband syndrome 2	AD	6	3
BCS1L	Bjornstad syndrome, GRACILE syndrome, Leigh syndrome, Mitochondrial complex III deficiency, nuclear type 1	AR	42	37
BDP1*	Hearing loss	AD/AR	1	1
BSND	Sensorineural deafness with mild renal dysfunction, Bartter syndrome	AR	10	20
BTD	Biotinidase deficiency	AR	170	247
C10ORF2	Perrault syndrome, Mitochondrial DNA depletion syndrome, Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 3	AD/AR	37	80
CABP2	Deafness	AR	1	6
CACNA1D	Primary aldosteronism, seizures, and neurologic abnormalities, Sinoatrial node dysfunction and deafness	AD/AR	7	8
CATSPER2*		AR	2	7
CCDC50	Deafness	AD	1	4
CD151	Raph blood group, Nephropathy with pretibial epidermolysis bullosa and deafness	AR	1	3
CD164	Deafness, autosomal dominant 66	AD	1	1
CDC14A	Deafness, autosomal recessive 105	AR	7	9
CDC42*	Takenouchi-Kosaki syndrome, Noonan-syndrome like phenotype	AD	11	9
CDH23	Deafness, Usher syndrome, type 1D	AR	94	358
CDK9		AR		1
CDKN1C	Beckwith-Wiedemann syndrome, IMAGE syndrome	AD	35	81
CEACAM16	Deafness	AD/AR	4	4
CEP250	Cone rod dystrophy and hearing loss	AR		5
CEP78	Cone rod dystrophy and hearing loss	AR	7	9
CHD7	Isolated gonadotropin-releasing hormone deficiency, CHARGE syndrome	AD	276	860
CHSY1	Temtamy preaxial brachydactyly syndrome	AR	6	16
CIB2	Deafness, Usher syndrome type IJ	AR	5	18
CISD2*	Wolfram syndrome 2	AR	2	4
CLDN14	Deafness	AR	11	12
CLIC5	Deafness	AR	1	2
CLPP	Deafness	AR	4	13
CLRN1	Retinitis pigmentosa, Usher sydnrome, type 3A	AR	24	39
COCH	Deafness	AD	14	29
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
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/AR	180	561
COL4A3	Alport syndrome, Hematuria, benign familial	AD/AR	123	264
COL4A4	Alport syndrome, Hematuria, benign familial	AD/AR	110	232
COL4A5	Alport syndrome, X-linked	XL	704	992
COL4A6	Deafness, with cochlear malformation	XL	11	5
COL9A1	Stickler syndrome, type IV	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
CRYM	Deafness	AD	2	4
DCAF17	Woodhouse-Sakati syndrome	AR	14	14
DCDC2	Deafness, Nephronophthisis, Sclerosing cholangitis, neonatal	AR	13	9
DFNA5	Deafness	AD	7	13
DFNB31	Usher syndrome, type 2D, Deafness, autosomal recessive 31	AR	12	31
DFNB59	Deafness	AR	12	20
DIABLO	Deafness	AD	1	2
DIAPH1	Seizures, cortical blindness, and microcephaly syndrome (SCBMS), Deafness, autosomal dominant 1	AD/AR	10	15
DIAPH3	Non-syndromic sensorineural deafness	AD	1	9
DLX5	Split-hand/foot malformation with sensorineural hearing loss, Split-hand/foot malformation	AD/AR	3	9
DMXL2	Deafness, autosomal dominant, 71, Polyendocrine-polyneuropathy syndrome, Epileptic encephalopathy, early infantile	AD/AR	2	6
DNMT1	Neuropathy, hereditary sensory, Cerebellar ataxia, deafness, and narcolepsy	AD	9	20
DSPP	Dentin dysplasia, Dentinogenesis imperfecta, Deafness, with dentinogenesis imperfecta	AD	11	53
EDN3	Hirschsprung disease, Central hypoventilation syndrome, congenital, Waardenburg syndrome	AD/AR	7	21
EDNRA	Mandibulofacial dysostosis with alopecia	AD	2	4
EDNRB	Hirschsprung disease, ABCD syndrome, Waardenburg syndrome	AD/AR	12	66
EFTUD2	Mandibulofacial dysostosis with microcephaly, Esophageal atresia, syndromic	AD	45	99
EIF3F	Intellectual disability, autosomal recessive	AR
ELMOD3	Deafness	AR	1	2
EPS8	Deafness	AR	2	2
EPS8L2	Deafness, autosomal recessive 106	AR	2	2
ESPN*	Deafness, Deafness, autosomal recessive 36	AD/AR	12	15
ESRRB	Deafness	AR	12	19
EYA1	Otofaciocervical syndrome, Branchiootic syndrome, Branchiootorenal syndrome	AD	56	218
EYA4	Dilated cardiomyopathy (DCM), Deafness, autosomal dominant 10	AD	15	28
FAM136A*	Sensorineural hearing loss	AD	1	2
FAM65B	Deafness, Deafness, autosomal recessive 104	AD/AR	1	2
FDXR	Auditory neuropathy and optic atrophy	AR	5	19
FGF3	Deafness, congenital with inner ear agenesis, microtia, and microdontia	AR	13	20
FGFR2	Apert syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome, Lacrimoauriculodentodigital syndrome, Beare-Stevenson cutis gyrata syndrome, Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis, Craniofacial-skeletal-dermatological dysplasia, Crouzon syndrome, Bent bone dysplasia	AD	100	154
FGFR3	Lacrimoauriculodentodigital syndrome, Muenke syndrome, Crouzon syndrome with acanthosis nigricans, Camptodactyly, tall stature, and hearing loss (CATSHL) syndrome, Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia type 1, Thanatophoric dysplasia type 2, SADDAN	AD/AR	54	77
FITM2	Dystonia, Deafness	AR		1
FOXC1	Axenfeld-Rieger syndrome, Iridogoniodysgenesis, Peters anomaly	AD	46	135
FOXI1	Pendred syndrome, Enlarged vestibular aqueduct	AR	1	11
GATA3	Hypomagnesemia, renal, Hypoparathyroidism, sensorineural deafness, and renal dysplasia	AD	22	86
GDF6	Microphthalmia, isolated 4, Microphthalmia, isolated, with coloboma 6, Coloboma, ocular, Klippel-Feil syndrome 1, autosomal dominant, Leber congenital amaurosis 17	AD/AR	9	21
GIPC3	Deafness	AR	9	20
GJA1*	Oculodentodigital dysplasia mild type, Oculodentodigital dysplasia severe type, Syndactyly type 3	AD/AR	31	107
GJB2	Bart-Pumphrey syndrome, Keratoderma, palmoplantar, with deafness, Vohwinkel syndrome, Hystrix-like ichthyosis with deafness, Keratitis-icthyosis-deafness syndrome, Deafness, autosomal recessive 1A	AD/AR/Digenic	133	405
GJB3	Deafness, Erythrokeratodermia variabilis et progressiva 1, Deafness, autosomal dominant 2B	AD/AR	11	40
GJB6	Deafness, autosomal dominant 3B, Ectodermal dysplasia, hidrotic (Clouston syndrome), Deafness, autosomal recessive 1B	AD/AR	10	33
GPSM2	Chudley-McCullough syndrome	AR	18	11
GREB1L	Congenital anomalies of the kidney and urinary tract, Renal hypodysplasia/aplasia 1	AD	15	36
GRHL2	Ectodermal dysplasia/short stature syndrome, Deafness, autosomal dominant 28, Corneal dystrophy, posterior polymorphous	AD/AR	12	12
GRXCR1	Deafness	AR	8	9
GRXCR2	Deafness	AR	1	2
HARS*	Charcot-Marie-Tooth disease, axonal, type 2W, Usher syndrome, type 3B	AD/AR	6	12
HARS2	Perrault syndrome	AR	7	3
HGF	Deafness	AR	4	10
HOMER2	Deafness	AD	2	1
HOXA2		AR	3	5
HOXB1	Facial paresis, hereditary congenital	AR	3	6
HSD17B4	Perrault syndrome, D-bifunctional protein deficiency	AR	60	99
ILDR1	Deafness, autosomal recessive 42	AR	8	27
KARS	Charcot-Marie-Tooth disease, Deafness, autosomal recessive, Leukoencephalopathy	AR	9	23
KCNE1	Long QT syndrome, Jervell and Lange-Nielsen syndrome	AD/AR/Digenic	11	46
KCNJ10	Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SESAME syndrome), Pendred syndrome, Enlarged vestibular aqueduct	AR/Digenic	13	29
KCNQ1	Short QT syndrome, Long QT syndrome, Atrial fibrillation, Jervell and Lange-Nielsen syndrome	AD/AR	298	631
KCNQ4	Deafness, autosomal dominant 2A	AD	28	37
KIT	Gastrointestinal stromal tumor, Piebaldism	AD	79	116
KITLG	Hyperpigmentation with or without hypopigementation, familial progressive, Deafness, autosomal dominant 69, Waardenburg syndrome	AD/AR	6	10
KMT2D	Kabuki syndrome	AD	350	670
LARS2	Perrault syndrome, Hydrops, lactic acidosis, and sideroblastic anemia (HLASA)	AR	14	14
LHFPL5	Deafness	AR	7	10
LHX3	Pituitary hormone deficiency, combined	AR	9	16
LMX1A	Hearing loss	AD/AR	1	4
LOXHD1	Deafness, autosomal recessive 77	AR	26	60
LRP2	Donnai-Barrow syndrome, Faciooculoacousticorenal syndrome	AR	24	38
LRTOMT	Deafness, autosomal recessive 63	AR	7	17
MAN2B1	Mannosidosis, alpha B, lysosomal	AR	63	149
MANBA	Mannosidosis, lysosomal	AR	16	19
MARVELD2	Deafness	AR	9	17
MASP1	3MC syndrome	AR	11	22
MCM2	Deafness, autosomal dominant 70	AD	3	1
MET	Deafness, Renal cell carcinoma, papillary, Osteofibrous dysplasia, susceptibility to	AD/AR	20	34
MGP	Keutel syndrome	AR	5	8
MIR96	Deafness	AD	2	4
MITF	Tietz albinism-deafness syndrome, Waardenburg syndrome, Coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness (COMMAD)	AD/AR	32	58
MPZL2	Sensorineural hearing loss	AR		4
MSRB3	Deafness	AR	5	2
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
MYH14	Peripheral neuropathy, myopathy, hoarseness, and hearing loss, Deafness, autosomal dominant 4	AD	7	44
MYH9	Sebastian syndrome, May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome, Macrothrombocytopenia and progressive sensorineural deafness, Deafness, autosomal dominant 17	AD	25	117
MYO15A	Deafness, autosomal recessive 3	AR	97	235
MYO3A	Deafness	AR	9	22
MYO6	Deafness, autosomal dominant, 22, Deafness, autosomal recessive 37	AD/AR	24	68
MYO7A	Deafness, autosomal dominant 11, Usher syndrome, type I, Deafness, autosomal recessive 2	AD/AR	239	515
NARS2	Combined oxidative phosphorylation deficiency	AR	12	12
NDP	Exudative vitreoretinopathy, Norrie disease	XL	31	167
NDRG1	Charcot-Marie-Tooth disease	AR	6	8
NEFL	Charcot-Marie-Tooth disease	AD	24	40
NF2	Schwannomatosis, Neurofibromatosis	AD	66	433
NLRP3	Neonatal onset multisystem inflammatory disease (NOMID), Muckle-Wells syndrome, Chronic infantile neurologic cutaneous articular (CINCA) syndrome, Familial cold-induced autoinflammatory syndrome 1, Deafness	AD	20	136
NOG	Tarsal-carpal coalition syndrome, Multiple synostosis syndrome, Stapes ankylosis with broad thumb and toes (Teunissen-Cremers syndrome), Symphalangism, proximal, Brachydactyly type B2	AD	20	63
NR2F1	Bosch-Boonstra optic atrophy syndrome	AD	23	34
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
OSBPL2	Deafness	AD	2	3
OTOA#*	Deafness	AR	19	28
OTOF	Neuropathy, Deafness, autosomal recessive 9	AR	107	163
OTOG	Deafness	AR	18	3
OTOGL	Deafness, autosomal recessive 84B	AR	26	23
P2RX2	Deafness	AD	2	4
PAX1	Otofaciocervical syndrome 2	AR	2	10
PAX3	Craniofacial-deafness-hand syndrome, Waardenburg syndrome, type 1, Waardenburg syndrome, type 3	AD/AR	54	149
PCDH15	Deafness, Usher syndrome, type 1D	AR/Digenic	113	118
PCGF2	Turnpenny-Fry syndrome	AD		1
PDE1C	Hearing loss	AD	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
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
PEX2	Zellweger syndrome, Peroxisome biogenesis disorder	AR	16	18
PEX26	Adrenoleukodystrophy, neonatal, Zellweger syndrome, Peroxisome biogenesis disorder	AR	13	27
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
PMP22	Neuropathy, inflammatory demyelinating, Roussy-Levy syndrome, Dejerine-Sottas disease, Neuropathy, hereditary, with liability to pressurve palsies, Charcot-Marie-Tooth disease	AD/AR	49	165
PNPT1*	Combined oxidative phosphorylation deficiency, 13, Deafness, autosomal recessive 70, Spinocerebellar ataxia	AD/AR	11	13
POLR1C#	Treacher Collins syndrome	AR	17	21
POLR1D	Treacher Collins syndrome	AD/AR	9	26
POU3F4	Deafness	XL	25	80
POU4F3	Deafness	AD	9	33
PRPS1*	Phosphoribosylpyrophosphate synthetase I superactivity, Arts syndrome, Charcot-Marie-Tooth disease, X-linked recessive, 5, Deafness, X-linked 1	XL	27	32
PTPRQ	Deafness, autosomal dominant 73, Deafness, autosomal recessive 84	AD/AR	10	34
RAI1	Smith-Magenis syndrome	AD	37	112
RDX*	Deafness, autosomal recessive 24	AR	6	10
REST	Fibromatosis, gingival, 5, Wilms tumor 6, susceptibility to	AD	3	16
RMND1*	Combined oxidative phosphorylation deficiency	AR	17	15
ROR1	Deafness, autosomal recessive 108		3	2
RPS6KA3	Coffin-Lowry syndrome, Intellectual developmental disorder	XL	65	171
S1PR2	Deafness, autosomal recessive 68	AR	2	3
SALL1*	Townes-Brocks syndrome 1	AD	31	87
SALL4	Acro-renal-ocular syndrome, Duane-radial ray/Okihiro syndrome	AD	21	56
SEMA3E	CHARGE syndrome	AD	1	4
SERAC1	3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome	AR	22	52
SERPINB6	Deafness	AR	2	3
SH3TC2	Mononeuropathy of the median nerve, Charcot-Marie-Tooth disease	AR	63	89
SIX1	Branchiootic syndrome, Branchiootorenal syndrome, Deafness, autosomal dominant 23	AD	11	19
SIX2			1	9
SIX5	Branchiootorenal syndrome	AD	3	10
SLC17A8	Deafness	AD	1	8
SLC19A2	Thiamine-responsive megaloblastic anemia syndrome	AR	14	51
SLC22A4	Hearing loss	AR		2
SLC26A4	Deafness, Pendred syndrome, Enlarged vestibular aqueduct	AR	181	548
SLC26A5	Deafness, autosomal recessive 61	AR	2	7
SLC29A3	Histiocytosis-lymphadenopathy plus syndrome, Dysosteosclerosis	AR	17	25
SLC33A1*	Congenital cataracts, hearing loss, and neurodegeneration, Spastic paraplegia 42, autosomal dominant	AD/AR	6	7
SLC44A4	Deafness, autosomal dominant, 72	AD	1
SLC4A11	Cryohydrocytosis, Corneal dystrophy, Fuchs endothelial 4, Corneal endothelial dystrophy 2, autosomal recessive, Corneal endothelial dystrophy and perceptive deafness	AD/AR	22	95
SLC52A2	Brown-Vialetto-Van Laere syndrome	AR	27	25
SLC52A3	Fazio-Londe disease, Brown-Vialetto-Van Laere syndrome	AR	30	42
SLITRK6	Deafness and myopia	AR	3	5
SMAD4	Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Polyposis, juvenile intestinal, Myhre dysplasia, Hereditary hemorrhagic telangiectasia	AD	179	143
SMPX	Deafness	XL	8	14
SNAI2	Waardenburg syndrome, Piebaldism	AR	2	4
SOX10	Peripheral demyelinating neuropathy, central dysmyelination, Waardenburg syndrome, and Hirschsprung disease, Kallmann syndrome	AD	56	148
SPATA5	Developmental delay with or without dysmorphic facies and autism, Epilepsy, hearing loss, and mental retardation syndrome (EHLMRS)	AR	27	27
STAG2	Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder	XL	6	14
STRC#*	Deafness, autosomal recessive 16	AR	31	85
SUCLA2	Mitochondrial DNA depletion syndrome	AR	9	29
SUCLG1	Mitochondrial DNA depletion syndrome	AR	12	28
SYNE4	Deafness	AR	6	2
SYT2*	Myasthenic syndrome, congenital 7, presynaptic	AD	3	3
TBC1D24	Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS) syndrome, Deafness, autosomal dominant, 65, Myoclonic epilepsy, infantile, familial, Epileptic encephalopathy, early infantile, 16, Deafness, autosomal recessive 86	AD/AR	43	55
TBL1X	Congenital hypothyroidism, Hearing loss		2	8
TBX1	Conotruncal anomaly face syndrome	AD	17	72
TCOF1	Treacher Collins syndrome	AD	50	330
TECTA	Deafness, autosomal dominant 8/12, Deafness, autosomal recessive 21	AD/AR	36	120
TFAP2A	Branchiooculofacial syndrome	AD	23	42
TIMM8A*	Mohr-Tranebjaerg syndrome, Jensen syndrome, Opticoacoustic nerve atrophy with dementia	XL	11	21
TJP2	Cholestasis, progressive familial intrahepatic, Hypercholanemia, familial, Deafness, autosomal dominant 51	AD/AR	25	27
TMC1	Deafness, autosomal dominant 36, Deafness, autosomal recessive 7	AD/AR	33	91
TMEM126A	Optic atrophy	AR	3	1
TMEM132E	Hearing loss	AR		1
TMIE	Deafness	AR	9	10
TMPRSS3	Deafness	AR	25	82
TNC	Deafness	AD	3	6
TPRN	Deafness, autosomal recessive 79	AR	6	12
TRIOBP	Deafness	AR	22	40
TRMU	Liver failure, infantile, Reversible infantile respiratory chain deficiency	AR	20	21
TRRAP	Developmental delay with or without dysmorphic facies and autism	AD		19
TSHZ1	Aural atresia, congenital	AD	2	4
TSPEAR		AR	2	7
TUBB4B	Leber congenital amaurosis, Hearing loss	AD	2	3
TYR*	Albinism, oculocutaneous	AR	77	441
UBR1	Johanson-Blizzard syndrome	AR	11	71
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
WBP2	Deafness, autosomal recessive 107	AR	3	3
WFS1	Wolfram syndrome, Wolfram-like syndrome, autosomal dominant, Deafness, autosomal dominant 6/14/38, Cataract 41	AD/AR	69	362
XYLT2	Spondyloocular syndrome	AR	2	10

Notes

# A gene marked with this symbol has suboptimal coverage. Fewer than 90% of the gene’s target nucleotides are covered at >20x with mapping quality (MQ>20) reads. Certain exons listed in the Test Limitations section may be excluded if they cannot be reliably sequenced.

* Some or all regions of the gene are duplicated in the genome, which may reduce sensitivity for variant detection. Genes marked with * or # may not be available as single-gene tests.

Abbreviations & References

Gene → HGNC-approved gene symbol.
Inheritance → autosomal dominant (AD), autosomal recessive (AR), mitochondrial (mi), X-linked (XL), X-linked dominant (XLD), X-linked recessive (XLR).
ClinVar → count of pathogenic/likely pathogenic variants (ClinVar).
HGMD → count of variants with possible disease association (HGMD).
Associated phenotypes → compiled from CGD or Mitomap.

Non-coding variants covered by Comprehensive Hearing Loss and Deafness Panel

Gene	Genomic location HG19	HGVS	RefSeq	RS-number
AIFM1	ChrX:129274636	c.697-44T>G	NM_004208.3
AIFM1	ChrX:129299753	c.-123G>C	NM_004208.3	rs724160014
ANKH	Chr5:14871567	c.-11C>T	NM_054027.4
BCS1L	Chr2:219524871	c.-147A>G	NM_004328.4
BCS1L	Chr2:219525123	c.-50+155T>A	NM_004328.4	rs386833855
BTD	Chr3:15683399	c.310-15delT	NM_000060.2	rs587783008
CDKN1C	Chr11:2905209	c.*5+20G>T	NM_000076.2	rs760540648
CHD7	Chr8:61734568	c.2836-15C>G	NM_017780.3
CHD7	Chr8:61757794	c.5051-15T>A	NM_017780.3
CHD7	Chr8:61763034	c.5405-18C>A	NM_017780.3	rs199981784
CHD7	Chr8:61763035	c.5405-17G>A	NM_017780.3	rs794727423
CHD7	Chr8:61763039	c.5405-13G>A	NM_017780.3	rs1131690787
CLRN1	Chr3:150660197	c.254-649T>G	NM_001195794.1	rs976853535
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
COL4A3	Chr2:228145145	c.2224-11C>T	NM_000091.4
COL4A3	Chr2:228168708	c.4028-27A>G	NM_000091.4
COL4A3	Chr2:228173596	c.4463-18dupA	NM_000091.4	rs769590145
COL4A4	Chr2:227875240	c.4334-23A>G	NM_000092.4
COL4A5	ChrX:107813924	c.385-719G>A	NM_033380.2	rs104886396
COL4A5	ChrX:107816792	c.466-12G>A	NM_033380.2	rs104886414
COL4A5	ChrX:107820077	c.609+875G>T	NM_033380.2
COL4A5	ChrX:107821295	c.646-12_646-11delTT	NM_033380.2	rs104886436
COL4A5	ChrX:107834930	c.1423+57dupC	NM_033380.2	rs104886328
COL4A5	ChrX:107838719	c.1424-20T>A	NM_033380.2	rs281874668
COL4A5	ChrX:107845097	c.2042-18A>G	NM_033380.2	rs104886341
COL4A5	ChrX:107849932	c.2245-40A>G	NM_033380.2
COL4A5	ChrX:107849958	c.2245-14T>A	NM_033380.2
COL4A5	ChrX:107852872	c.2395+2750A>G	NM_033380.2
COL4A5	ChrX:107908726	c.3374-11C>A	NM_033380.2	rs104886387
COL4A5	ChrX:107933678	c.4529-2300T>G	NM_033380.2
COL4A5	ChrX:107935633	c.4529-345A>G	NM_033380.2
COL4A5	ChrX:107938272	c.4821+121T>C	NM_033380.2	rs104886423
COL4A5	ChrX:107938337	c.4822-152dupT	NM_033380.2
COL4A5	ChrX:107938346	c.4822-151_4822-150insT	NM_033380.2	rs397515494
COL4A5	ChrX:107845097	c.2042-18A>G	NM_033380.2	rs104886341
COL4A5	ChrX:107849932	c.2245-40A>G	NM_033380.2
COL4A5	ChrX:107849958	c.2245-14T>A	NM_033380.2
COL4A5	ChrX:107852872	c.2395+2750A>G	NM_033380.2
COL4A5	ChrX:107908726	c.3374-11C>A	NM_033380.2	rs104886387
COL4A5	ChrX:107933678	c.4529-2300T>G	NM_033380.2
COL4A5	ChrX:107935633	c.4529-345A>G	NM_033380.2
COL4A5	ChrX:107938272	c.4821+121T>C	NM_033380.2	rs104886423
COL4A5	ChrX:107938337	c.4822-152dupT	NM_033380.2
COL4A5	ChrX:107938346	c.4822-151_4822-150insT	NM_033380.2	rs397515494
DCAF17	Chr2:172305176	c.322-14delC	NM_025000.3	rs201494527
DFNA5	Chr7:24746007	c.991-15_991-13delTTC	NM_004403.2	rs727505273
EDN3	Chr20:57875849	c.-19C>A	NM_000114.2	rs375594972
EYA1	Chr8:72156939	c.1051-12T>G	NM_000503.4
EYA1	Chr8:72211483	c.640-15G>A	NM_000503.4
EYA4	Chr6:133833847	c.1282-12T>A	NM_004100.4
EYA4	Chr6:133833997	c.1341-19T>A	NM_004100.4
FGFR2	Chr10:123099960	c.*139411C>T	.
FOXC1	Chr6:1610252	c.-429C>G	NM_001453.2	rs77888940
GJB2	Chr13:20763744	c.-22-2A>C	NM_004004.5	rs201895089
GJB2	Chr13:20766920	c.-23+2T>A	NM_004004.5
GJB2	Chr13:20766921	c.-23+1G>A	NM_004004.5	rs80338940
GJB2	Chr13:20766922	c.-23G>T	NM_004004.5	rs786204734
GJB2	Chr13:20767158	c.-259C>T	NM_004004.5
GJB2	Chr13:20767159	c.-260C>T	NM_004004.5
GRHL2	Chr8:102505149	c.20+133delA	NM_024915.3
GRHL2	Chr8:102505272	c.20+257delT	NM_024915.3
GRHL2	Chr8:102505561	c.20+544G>T	NM_024915.3
GRXCR1	Chr4:42965170	c.627+19A>T	NM_001080476.2	rs201824235
HGF	Chr7:81384504	c.482+1991_482+2000delGATGATGAAA	NM_000601.4	rs900334407
HGF	Chr7:81384516	c.482+1986_482+1988delTGA	NM_000601.4
HSD17B4	Chr5:118837725	c.1285-11C>G	NM_001199291.1	rs779466683
KCNJ10	Chr1:160039811	c.-1+1G>T	NM_002241.4	rs796052606
KCNQ1	Chr11:2484803			rs2074238
KMT2D	Chr12:49428461	c.10356-12G>A	NM_003482.3
MYO3A	Chr10:26409593	c.1777-12G>A	NM_017433.4
MYO6	Chr6:76593963	c.2417-1758T>G	NM_004999.3
MYO7A	Chr11:76841633	c.-46-2A>G
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
NF2	Chr22:30050946	c.516+232G>A	NM_000268.3
OPA1	Chr3:193334932	c.449-34dupA	NM_130837.2
OPA1	Chr3:193374829	c.2179-40G>C	NM_130837.2
PAX3	Chr2:223085913	c.958+28A>T	NM_181459.3
PCDH15	Chr10:56560684	c.-29+1G>C	NM_001142763.1
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
PMP22	Chr17:15162523	c.79-13T>A	NM_000304.3
REST	Chr4:57793760	c.983-2247C>G	NM_005612.4
RPS6KA3	ChrX:20191268	c.1228-279T>G	NM_004586.2
RPS6KA3	ChrX:20213274	c.326-11A>G	NM_004586.2
SERAC1	Chr6:158576548	c.92-165C>T	NM_032861.3
SERAC1	Chr6:158576622	c.92-239G>C	NM_032861.3
SH3TC2	Chr5:148406329	c.2873-14T>A	NM_024577.3
SH3TC2	Chr5:148422415	c.386-15G>A	NM_024577.3
SLC26A4	Chr7:107301201	c.-103T>C	NM_000441.1	rs60284988
SLC26A4	Chr7:107301244	c.-60A>G	NM_000441.1	rs545973091
SLC26A4	Chr7:107301301	c.-4+1G>C	NM_000441.1
SLC26A4	Chr7:107301305	c.-4+5G>A	NM_000441.1	rs727503425
SLC26A4	Chr7:107323842	c.918+45_918+47delCAA	NM_000441.1
SLC26A4	Chr7:107330533	c.1150-35_1150-28delTTTGTAGG	NM_000441.1
SLC26A4	Chr7:107334836	c.1264-12T>A	NM_000441.1
SLC26A4	Chr7:107336364	c.1438-7dupT	NM_000441.1	rs754734032
SLC26A4	Chr7:107341513	c.1708-27_1708-11delTAAGTAACTTGACATTT	NM_000441.1
SLC26A4	Chr7:107350439	c.2090-52_2090-49delCAAA	NM_000441.1
SLC29A3	Chr10:73122778	c.*413G>A	NM_018344.5
SLC4A11	Chr20:3211931	c.1077+26_1077+44delCGGCAGGGTCGGCGGGGGC	NM_001174090.1
SLC52A2	Chr8:145582843	c.-110-1G>A	NM_024531.4
SNAI2	Chr8:49833972	c.-149_-148delCGinsTA	NM_003068.4
SOX10	Chr22:38412215	c.-31954C>T	NM_006941.3	rs606231342
SOX10	Chr22:38412781	c.-32520C>G	NM_006941.3	rs533778281
TBX1	Chr22:19743578	c.-777C>T	NM_080647.1
TBX1	Chr22:19743735	c.-620A>C	NM_080647.1	rs536892777
TIMM8A	ChrX:100601671	c.133-23A>C	NM_004085.3	rs869320666
TMC1	Chr9:75315577	c.362+18A>G	NM_138691.2
TYR	Chr11:88960973	c.1037-18T>G	NM_000372.4
UBR1	Chr15:43330355	c.1911+14C>G	NM_174916.2
UBR1	Chr15:43350639	c.1094-12A>G	NM_174916.2
UBR1	Chr15:43350640	c.1094-13A>G	NM_174916.2
UBR1	Chr15:43363136	c.529-13G>A	NM_174916.2
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

Legend

HGVS: Human Genome Variation Society nomenclature used to describe sequence variants (e.g., c.2678-15C>A).
RefSeq: Reference sequence accession (transcript) used for variant annotation (NCBI RefSeq, e.g., NM_000138.4).
RS-number: dbSNP reference ID (rsID) for the variant when available.
Genomic location (HG19): Chromosomal coordinates based on the human genome build GRCh37/hg19.

Genetic testing for this gene is performed by taking a blood sample or by taking genetic material from inside the cheeks (with a swab), and can be done:

By taking the sample at Diagnostiki Athinon. Book your appointment in real-time and purchase the test online
By taking the sample at home. We send you all the necessary collection materials to your home via courier. The courier also returns the sample to the laboratory. Purchase the test online

Test Strengths

The test is characterized by the following strengths:

Analysis is performed in a CAP-accredited laboratory with the participation of CLIA-certified personnel.
Advanced sequencing technologies, high-performance target enrichment methods, and precise bioinformatics pipelines ensure superior analytical performance.
Gene panels are carefully designed to be clinically effective and scientifically validated.
In some panels, the entire mitochondrial genome is included (see Panel Content section).
Approximately 2,000 non-coding disease-causing variants are covered in the clinical-grade NGS assay (see Non-coding disease-causing variants covered by this panel in the Panel Content section).
A rigorous variant classification system is applied.
A systematic interpretation workflow, supported by proprietary software, enables accurate and traceable processing of NGS data.
Comprehensive and clinically meaningful reports are provided.

Test Limitations

Specific technical and biological limitations apply:

Certain exons are excluded from the panel because they do not achieve adequate high-quality sequencing coverage. These include: OTOA (exons 22-27), PDZD7 (exon 10), POLR1C (exon 9), STRC (exons 1-18). Variants can be detected in STRC exons 19-29, but interpretation is limited due to strong sequence similarity with other genomic regions. However, complete deletions of the STRC gene can be reliably identified.
Genes with suboptimal coverage are marked with a number sign (#), while those with partial or complete segmental duplications overlapping UCSC pseudogene regions are marked with an asterisk (*).
A gene is considered to have suboptimal coverage when more than 90% of its target nucleotides are not covered at a depth of greater than 20x with mapping quality score (MQ > 20) reads. In such cases, detection of variants may be limited.

This test does not detect:

Complex inversions
Gene conversions
Balanced translocations
Repeat expansion disorders, unless otherwise specified
Non-coding variants beyond ±20 base pairs from the exon–intron boundary, unless otherwise indicated
The complete mitochondrial genome in all panels (see Panel Content section

This test may not reliably detect:

Low-level mosaicism in nuclear genes (variants with a minor allele fraction of ~14.6% are detected with 90% probability)
Stretches of mononucleotide repeats
Low-level heteroplasmy in mtDNA (>90% detected at 5% level)
Insertions or deletions larger than 50 bp
Single-exon deletions or duplications
Variants within pseudogene regions or duplicated genomic segments
Disease-causing mtDNA variants not present in blood; in such cases, post-mitotic tissue (e.g., skeletal muscle) may be required to establish a molecular diagnosis

For further details, please refer to the Bioinformatics & Performance section.

Bioinformatics

The target region for each gene encompasses the coding exons as well as ±20 base pairs from the exon–intron boundaries. In addition, the panel may include non-coding and regulatory variants, as listed in the “Non-coding variants covered by the panel” section. Specific regions of certain gene(s) may be excluded from analysis if noted in the “Test limitations” section. When the test includes the mitochondrial genome, the target region also comprises the complete set of mitochondrial genes.

Sequencing data is processed through a proprietary analysis and annotation pipeline that integrates state-of-the-art algorithms and industry-standard software solutions. Multiple quality control steps are embedded throughout the workflow to ensure the accuracy, validity, and consistency of the results. The pipeline is optimized to maximize sensitivity without compromising specificity.

For variant interpretation, the system incorporates data from multiple reference populations and mutation databases, including (but not limited to) the 1000 Genomes Project, gnomAD, ClinVar, and HGMD. In silico tools such as SIFT, PolyPhen, and MutationTaster are also applied to support the classification of missense variants.

All findings are summarized in a clear and detailed clinical report. This report includes sequencing quality metrics, gene-level coverage information, and highlights any regions where coverage is limited (<20x for nuclear genes and <1000x for mtDNA, when applicable). This ensures transparency and supports accurate clinical decision-making.

Test Performace

The genes included in this panel have been carefully selected based on evidence from scientific literature, mutation databases, and accumulated clinical expertise.

All panels are derived from a high-quality, clinical-grade NGS assay. Details regarding the detection of different types of genetic alterations are provided in the sequencing and detection performance table (see Table).

The assay has been validated for several sample types, including EDTA blood, isolated DNA (excluding DNA from formalin-fixed paraffin-embedded tissue), saliva, and dried blood spots (filter cards). These sample types were chosen to maximize the probability of obtaining high-quality DNA. The diagnostic yield may vary depending on the assay performed, the referring healthcare professional, the hospital, and the country in which the test is conducted. The Plus Analysis further enhances the chance of reaching a genetic diagnosis, as large deletions and duplications cannot be detected by sequencing alone. This approach integrates both sequencing and deletion/duplication (copy number variant, CNV) analysis.

The performance metrics shown below are based on initial validation studies at an accredited clinical laboratory, with equivalent results confirmed across additional laboratory sites.

Performance of a high-quality, clinical-grade NGS sequencing assay for panels

Variant type	Sensitivity % (TP/(TP+FN))	Specificity %
Single-nucleotide variants (SNVs)	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 deletion (het)	100% (20/20)	NA
1 exon deletion (homo)	100% (5/5)	NA
1 exon deletion (het or homo)	100% (25/25)	NA
2-7 exon deletion (het or homo)	100% (44/44)	NA
1-9 exon duplication (het or homo)	75% (6/8)	NA
Simulated CNV detection
5 exons del/dup	98.7%	100.00%
Microdeletions/-duplications (n=37)
Size range (0.1–47 Mb)	100% (25/25)

Coverage metrics

Mean sequencing depth	143X
Nucleotides with >20x coverage (%)	99.86%

Performance of Mitochondrial Sequencing Assay

Variant type/condition	Sensitivity %	Specificity %
Analytic validation (n=4 samples)
SNVs Heteroplasmic (45-100%)	100% (50/50)	100%
SNVs Heteroplasmic (35-45%)	100% (87/87)	100%
SNVs Heteroplasmic (25-35%)	100% (73/73)	100%
SNVs Heteroplasmic (15-25%)	100% (77/77)	100%
SNVs Heteroplasmic (10-15%)	100% (74/74)	100%
SNVs Heteroplasmic (5-10%)	100% (3/3)	100%
SNVs Heteroplasmic (<5%)	50% (2/4)	100%
Clinical validation (n=76 samples)
SNVs Heteroplasmic (45-100%)	100% (1940/1940)	100%
SNVs Heteroplasmic (35-45%)	100% (4/4)	100%
SNVs Heteroplasmic (25-35%)	100% (3/3)	100%
SNVs Heteroplasmic (15-25%)	100% (3/3)	100%
SNVs Heteroplasmic (10-15%)	100% (9/9)	100%
SNVs Heteroplasmic (5-10%)	92.3% (12/13)	99.98%
SNVs Heteroplasmic (<5%)	88.9% (48/54)	99.93%
Indels 1-10bp (het 45-100%)	100% (32/32)	100%
Indels 1-10bp (het 5-45%)	100% (3/3)	100%
Indels 1-10bp (het <5%)	100% (5/5)	99.997%
Simulation data
Indels 1-24bp Homoplasmic (100%)	100% (17/17)	99.98%
Indels 1-24bp Heteroplasmic (50%)	100% (17/17)	99.99%
Indels 1-24bp Heteroplasmic (25%)	100% (17/17)	100%
Indels 1-24bp Heteroplasmic (20%)	100% (17/17)	100%
Indels 1-24bp Heteroplasmic (15%)	100% (17/17)	100%
Indels 1-24bp Heteroplasmic (10%)	94.1% (16/17)	100%
Indels 1-24bp Heteroplasmic (5%)	94.1% (16/17)	100%
CNVs (artificial mutations; n=1500)
Homoplasmic (100%) 500bp–5kb	100%	100%
Heteroplasmic (50%) 500bp–5kb	100%	100%
Heteroplasmic (30%) 500bp–5kb	100%	100%
Heteroplasmic (20%) 500bp–5kb	99.7%	100%
Heteroplasmic (10%) 500bp–5kb	99.0%	100%

Mitochondrial assay coverage metrics

Metric	Mean of medians	Median of medians
Mean sequencing depth MQ0 (clinical)	18224X	17366X
Nucleotides with >1000x MQ0 coverage (%)	100%
ρ0 cell line (=no mtDNA), mean sequencing depth	12X

Comprehensive clinical reports are delivered, designed to provide healthcare professionals with meaningful and actionable insights. Clinical interpretation requires a solid understanding of both clinical genetics and genetic principles. Reports are prepared by teams of molecular geneticists, medical experts, and other highly experienced professionals, who evaluate identified variants in the context of the patient’s phenotypic information provided in the requisition form.

The goal is to ensure that reports are clinically valuable and understandable to all healthcare providers, regardless of their level of training in genetics and genetics-related fields. Variant classification forms the foundation of clinical interpretation and guides patient management decisions. Classifications follow the ACMG 2015 guidelines. Sequence and copy number variants classified as pathogenic, likely pathogenic, or of uncertain significance (VUS) are confirmed using bidirectional Sanger sequencing or orthogonal methods such as qPCR/ddPCR whenever NGS quality metrics do not meet strict thresholds for a true positive call.

Each report includes tables for sequence and copy number variants, presenting essential information such as genomic coordinates, HGVS nomenclature, zygosity, allele frequencies, in silico predictions, phenotypic correlations, and variant classification. In addition, detailed descriptions are provided for the variant, the gene, and the related phenotypes, covering the gene’s role in human disease, mutation spectrum, variation in population cohorts, and links to associated conditions. References, abstracts, and variant databases are also cited, enabling healthcare providers to further evaluate reported findings if desired.

Reports are structured into two sections: primary findings and additional findings.

The primary findings consist of variants known to cause disease or rare variants that may explain the patient’s phenotype. The conclusion summarizes all available evidence and presents the rationale for classification.

Additional findings include variants that are not currently sufficient to explain the patient’s phenotype, based on existing knowledge. Examples include heterozygous variants in autosomal recessive genes, VUS in autosomal dominant genes (when a pathogenic or likely pathogenic variant already explains the phenotype), or risk alleles in genes included in the panel.

The identification of pathogenic or likely pathogenic variants in dominant disorders, or biallelic variants in recessive disorders, is considered molecular confirmation of the clinical diagnosis. In such cases, family testing may assist in risk assessment. Variants of uncertain significance are not recommended for patient management or family risk stratification. Genetic counseling is strongly advised.

Interpretation teams routinely analyze millions of variants across thousands of cases of rare diseases. With each case, internal knowledge of variant–phenotype relationships is enriched, enabling continuous refinement of classifications. As new evidence becomes available, previously reported variants may be reclassified. If a variant initially reported as a primary or secondary finding is later reclassified (for example, from VUS to pathogenic/likely pathogenic, or from pathogenic/likely pathogenic to VUS, likely benign, or benign), an updated statement is issued to the original ordering healthcare provider at no additional cost.