• Test code: 04113
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit

Invitae Nephronophthisis Panel

Test description

The Invitae Nephronophthisis Panel analyzes 27 genes that are associated with nephronophthisis (NPHP), which is characterized by renal and kidney cysts and end-stage renal disease. These genes were selected based on the available evidence to date to provide Invitae’s broadest test for NPHP.

Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Although there is no treatment currently available to halt the onset of renal failure, a diagnosis may help prepare the patient, family, and clinician for the possibility of renal transplantation. Identification of a disease-causing variant can inform recurrence-risk assessment and genetic counseling.

CEP290: Analysis includes the intronic variant NM_025114.3:c.2991+1655A>G.

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Primary panel (27 genes)


Alternative tests to consider

Nephronophthisis is a member of a class of disorders called ciliopathies. Ciliopathies are caused by pathogenic variants in genes that affect the function of cilia—the hair-like structures on the surface of cells. Ciliopathies share many overlapping symptoms, often making it difficult to distinguish between them based on clinical presentation alone.

The Invitae Sensory Ciliopathies Panel has been designed to provide a broad genetic analysis of this class of disorders and may be considered as an alternative to testing for a specific disorder. Depending on the individual’s clinical and family history, this broader panel may be appropriate. It can be ordered at no additional charge.

  • nephronophthisis (NPHP)
  • clinical subtypes are based on the age at which progression to end stage renal disease begins
    • adolescent type
    • infantile type
    • juvenile type

NPHP is characterized by renal cysts, inflammation, and fibrosis, all leading to early onset end-stage renal disease. Characteristic renal histology shows corticomedullary cysts, tubular basement membrane disruption, and tubulointerstitial nephropathy. Additional symptoms related to the renal disease present in NPHP include polyuria, polydipsia, fatigue, and anemia. Extra-renal manifestations are present in approximately 10% of individuals with NPHP and often involve the eye, brain, heart, and liver. Individuals with extra-renal involvement present with phenotypes that are more similar to other ciliopathy-related disorders, such as Senior-Loken syndrome, Joubert syndrome, Bardet-Biedl syndrome, and Meckel-Gruber syndrome. Extra-renal findings can include retinal degeneration, retinitis pigmentosa, cerebellar vermis hypoplasia, intellectual disability, ataxia, liver fibrosis, ventricular septal defect, molar tooth sign, and cone-shaped epiphyses.

Approximately 30% of patients with a clinical diagnosis of NPHP will have pathogenic variants in one of these genes. Pathogenic variants in NPHP1 account for 25% of cases while pathogenic variants in the remaining genes are much less common. In 70% of individuals with a clinical diagnosis of NPHP, no pathogenic variants will be identified. These data suggest that additional genes associated with NPHP are still unidentified.

NPHP is inherited in an autosomal recessive, oligogenic manner. OFD1-related Joubert syndrome is inherited in an X-linked manner.

Nephronophthisis is a fully penetrant disorder with symptoms that begin to manifest in infancy, childhood, or adolescence, based on the specific subtype present. Morbidity and mortality is related to the development of end stage renal disease (ESRD) and hepatobiliary disease. Most patients develop ESRD by the age of 13.

The incidence of NPHP in live births is estimated at approximately 1 in 50,000 in Canada and 1 in 922,000 in the United States.

Radiology findings are typically used to establish a clinical diagnosis of NPHP. Genetic testing should be considered to determine the molecular cause of disease in individuals with a clinical or suspected diagnosis of NPHP. Genetic testing can also be used to clarify uncertain radiology results, establish recurrence risk, provide disease prognosis, and potentially screen living donors for transplantation. Some of these genes have also been associated with extra-renal features such as retinal dystrophy, liver fibrosis, and pancreatic cysts. Identification of mutations in these genes can help to prepare the patient and clinician for the possibility of the involvement of other organ systems and may direct patient care.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
AHI1 NM_017651.4
ANKS6 NM_173551.4
CC2D2A NM_001080522.2
CEP164 NM_014956.4
CEP290* NM_025114.3
CEP83 NM_016122.2
DCDC2 NM_016356.4
GLIS2 NM_032575.2
IFT172 NM_015662.2
INVS NM_014425.3
IQCB1 NM_001023570.2
NEK8 NM_178170.2
NPHP1 NM_000272.3
NPHP3 NM_153240.4
NPHP4 NM_015102.4
OFD1 NM_003611.2
PKHD1 NM_138694.3
RPGRIP1L NM_015272.2
SDCCAG8 NM_006642.3
TCTN1 NM_001082538.2
TMEM216 NM_001173990.2
TMEM237 NM_001044385.2
TMEM67 NM_153704.5
TTC21B NM_024753.4
WDR19 NM_025132.3
XPNPEP3 NM_022098.3
ZNF423 NM_015069.3

CEP290: Analysis includes the intronic variant NM_025114.3:c.2991+1655A>G.