Inherited and genetic contributors to kidney disease are common across pediatric and adultnephrology and can present as chronic kidney disease (CKD), proteinuria, hematuria, nephrotic syndrome, tubulopathies, nephrolithiasis, cystic kidneydisease, hypertension, or congenital anomalies of the kidney and urinary tract(CAKUT). Phenotypes frequently overlap and acquired, or secondary diagnoses maymask an underlying monogenic cause.
The PreCheckHealth Services Comprehensive Kidney Disease Panel (153 genes) is a germline, targeted exome assay intended for constitutional DNA (e.g.,peripheral blood or saliva). The panel prioritizes genes with established relevance to glomerular disease (including Alport spectrum and podocytopathy),cystic kidney and ciliopathy-associated disease, tubulointerstitial and tubular transport disorders, complement-mediated kidney disease and thrombotic microangiopathy, and CAKUT and developmental renal disorders.
❖ Inherited UnexplainedCKD, especially with early onset, familyhistory, or atypical clinical course
❖ Hematuria and/orproteinuria (includingsuspected Alport spectrum disease)
❖ Steroid-resistant or familial nephrotic syndrome and suspected podocytopathy
❖ Cystic kidney disease, nephronophthisis, or other ciliopathy-associated renal disease
❖ Complement-mediated kidney disease (C3 glomerulopathy) or atypical hemolytic uremic syndrome(aHUS) / thrombotic microangiopathy
❖ CAKUT and renal developmental anomalies (including renal hypodysplasia, vesicoureteral reflux, duplex collecting system)
❖ Evaluation of at-risk relatives and, when clinically indicated, living donor risk assessment
1.Glomerular Basement Membrane Disorders (Alport Spectrum and Related)
❖ COL4A3, COL4A4,COL4A5, CD151
2. Podocytopathy and NephroticSyndrome (FSGS/SRNS)
❖ NPHS1, NPHS2, ACTN4,TRPC6, PLCE1, MYO1E, ARHGDIA, CD2AP, MAGI2, ANLN, FAT1, CRB2, WT1, LAMB2, DGKE,MYH9, PTPRO
3. Complement-Mediated Kidney Disease and Thrombotic Microangiopathy
❖ C3, CFB, CFH, CFI,CD46, THBD, DGKE
4. Cystic Kidney Disease and Ciliopathies (ADPKD/ARPKD/NPHP and Related)
❖ PKD1, PKD2, PKHD1,INVS, NPHP1, NPHP3, NPHP4, CEP164, CEP290, CEP83, CEP120, RPGRIP1L, SDCCAG8,TTC21B, IFT140, IFT27, TMEM67, TMEM231, TMEM237, TMEM216, TMEM138, WDPCP,WDR19, WDR73, ARL13B, ARL6, LZTFL1, B9D1, B9D2, BBS1, BBS2, BBS4, BBS5, BBS7,BBS9, BBS10, BBS12, MKKS, MKS1, CC2D2A, CPLANE1, PIBF1, TCTN2, TCTN3, TRAF3IP1,TRIM32, TULP3, ZNF423
5. Tubular Transport and Salt/WaterHandling Disorders
❖ SLC12A1, SLC12A3,KCNJ1, BSND, CLCN5, ATP6V0A4, ATP6V1B1, SLC4A1, SLC4A4, AQP2, AVPR2, SCNN1G,FXYD2, HSD11B2
6.Nephrolithiasis and Inborn Errors of Metabolism Affecting the Kidney
❖ AGXT, HOGA1, GRHPR,APRT, XDH, SLC3A1, SLC7A9, SLC22A12, SLC2A9, ENPP1, HPRT1, FAH, NHERF1
7.CAKUT and Renal Developmental Disorders
❖ PAX2, EYA1, SIX1,GREB1L, ROBO2, PBX1, NOTCH2, TBX18, ZMYM2, ITGA8, ITGA3, HPSE2, EMP2
8.Cholestatic/Trafficking and Multi system Syndromes with Renal Disease
❖ VIPAS39, VPS33B,SEC63, PRKCSH, TP53RK, COQ6, NEK1, NEK8, OFD1, OCRL, FAT4, ANKS6
Parameter Description
Genes Analyzed 153 kidney disease-related genes.
Technology Platform Illumina NGS (Hybrid-Capture Target Enrichment).
Coverage Metrics >98%bases at ≥20× read depth.
Variant TypesDetected SNVs and small indels (≤20 bp) within coding exons ±10 bp intronic boundaries.
Reference Genome GRCh38/hg38.
BioinformaticsPipeline SeqOne™,ACMG/AMP compliant.
Confirmatory Testing Sanger sequencing or orthogonal method as indicated.
Turnaround Time ~10 calendar days.
Quality Metrics Read quality≥Q30; allelic balance ≥0.3; minimum coverage 20×.
1. Diagnostic Clarity and Prognosis
❖ Clarifies the molecular etiology of CKD, proteinuria, hematuria, nephrotic syndrome, tubulopathy, cystic kidney disease, and CAKUT.
❖ Helps distinguish hereditary disease from secondary causes (e.g., immune-mediated, toxic, infectious, or metabolic), reducing diagnostic uncertainty and time to diagnosis.
2. Management, Surveillance, and CarePlanning
❖ Supports gene-informed monitoring (glomerular vs tubular vs cystic phenotypes) and informs when to broaden evaluation for syndromic disease.
❖ Can influence therapy selection and avoid ineffective interventions (e.g., identifying genetic steroid-resistant nephrotic syndrome where immunosuppression is less likely to be beneficial).
❖ Supports transplant-related planning (recurrence risk, donor evaluation in familial disease contexts) when appropriate.
3. Family Risk Assessment and Reproductive Planning
❖ Defines inheritance(AR/AD/X-linked) to guide recurrence risk counseling and cascade testing.
❖ Enables identification of at-risk relatives for earlier surveillance and intervention.
❖ RiskStratification and Diagnostic Clarification
Identify pathogenic or likely pathogenic variants underlying glomerular disorders (including COL4A3–COL4A5-associated disease), podocytopathies (e.g.,NPHS1/NPHS2/TRPC6/ACTN4 spectrum), cystic kidney and ciliopathy-associated conditions (e.g., PKD1/PKD2/PKHD1/NPHP genes), tubulopathies (e.g.,SLC12A1/SLC12A3/ATP6V0A4/ATP6V1B1/AQP2/AVPR2), complement-mediated kidney disease (e.g., CFH/CFI/C3/CD46), and CAKUT/developmental disorders (e.g.,PAX2/EYA1/SIX1/GREB1L/ROBO2). This supports transition from a descriptive phenotype to a definitive, gene-based diagnosis.
❖ FamilyRisk Assessment, Cascade Testing, and Reproductive Counseling
Clarify recurrence risk for families and identify at-risk relatives once a pathogenic variant is identified—particularly for recessive conditions (e.g., NPHS2, many ciliopathygenes), dominant progressive disease (e.g., UMOD, ACTN4, PKD1/PKD2), or X-linked forms (e.g., COL4A5, OCRL, OFD1). Results support targeted testing of relatives and, when indicated, partner evaluation for autosomal recessive disease risk.
❖ PersonalizedManagement, Surveillance, and Transplant-Relevant Planning
Use molecular findings to guide individualized monitoring (e.g., hematuria/proteinuria progression risk in COL4A3–COL4A5 disease), inform systemic evaluation when syndromic genes are implicated, and support transplant-related decisions(including evaluation of familial risk in potential living donors). For complement-mediated kidney disease and thrombotic microangiopathy genes, results may inform eligibility for targeted therapies and clinical trials, and help anticipate recurrence risk after transplantation.
This Comprehensive Kidney Disease Panel is best used as part of a multi-dimensional diagnostic strategy, often in combination with:
PharmacogeneticsTesting (for drug metabolism and gene-drug interaction
Match treatments to the patient’s metabolic phenotype (e.g., CYP2D6, CYP2C19, CYP3A5, CYP2C9), reducing the risk of adverse drug reactions and improving efficacy.
Together, these tools enable precision medicine teams to offer a fully customized, data-driven treatment plan for each patient.
Germline testing for kidney disease is an essential tool in precision medicine, enabling clinicians to identify molecular causes of CKD, glomerular disease, tubulopathies, cystic kidney disease, complement-mediated disorders, and CAKUT. When integrated with clinical evaluation, laboratory data (e.g., urinalysis, serologies), imaging, and pathology when appropriate, a targeted gene panel provides diagnostic clarity that can surpass clinical assessment alone.
With high analytic performance and curated gene–disease evidence, PreCheck Health Services delivers genomic insights that refine diagnosis, guide monitoring and management, and support decisions around transplant planning, systemic evaluation for syndromic disease, and reproductive risk management. Molecular findings also enable targeted cascade testing and clinically appropriate family evaluation.
This integrated approach supports earlier, more accurate, and individualized kidney care, improving long-term outcomes and enabling informed planning for patients and families.
The ComprehensiveKidney Disease Panel is designed to detect single-nucleotide variants (SNVs)and small insertions and deletions in 153 genes associated with hereditary kidney disease. Targeted regions for this panel include the coding exons and 10bp intronic sequences immediately adjacent to exon-intron boundaries. Extracted patient DNA is prepared using targeted hybrid capture, assignment of a unique index, and sequencing via Illumina sequencing by synthesis (SBS) technology.Data are aligned to the human genome build GRCh38. Variant interpretation is performed according to current American College of Medical Genetics andGenomics (ACMG) professional guidelines for the interpretation of germline sequence variants using the SeqOne pipeline.
ACE, ACTN4, AGT,AGTR1, AGXT, ALG5, ALG6, ALG8, ALG9, ANKS6, ANLN, APOA1, APOL1, APRT, AQP2,ARHGDIA, ARL13B, ARL6, ATP6V0A4, ATP6V1B1, AVPR2, B9D1, B9D2, BBS1, BBS10, BBS12,BBS2, BBS4, BBS5, BBS7, BBS9, BSND, C3, CC2D2A, CD151, CD2AP, CD46, CEP120,CEP164, CEP290, CEP83, CFAP418, CFB, CFH, CFI, CLCN5, CLDN16, CLDN19, COL4A3,COL4A4, COL4A5, COQ6, CPLANE1, CRB2, CUL3, DCDC2, DGKE, EMP2, ENPP1, EYA1, FAH,FAT1, FAT4, FGA, FXYD2, GLIS2, GREB1L, GRHPR, HNF1B, HOGA1, HPRT1, HPSE2,HSD11B2, IFT140, IFT27, INVS, IQCB1, ITGA3, ITGA8, KCNJ1, LAMB2, LMX1B, LZTFL1,MAFB, MAGI2, MKKS, MKS1, MUC1, MYH9, MYO1E, NEK1, NEK8, NHERF1, NOTCH2, NPHP1,NPHP3, NPHP4, NPHS1, NPHS2, OCRL, OFD1, PAX2, PBX1, PIBF1, PKD1, PKD2, PKHD1,PLCE1, PRKCSH, PTPRO, REN, ROBO2, RPGRIP1L, SCNN1G, SDCCAG8, SEC63, SIX1,SLC12A1, SLC12A3, SLC22A12, SLC2A9, SLC3A1, SLC4A1, SLC4A4, SLC5A2, SLC7A9,TBX18, TCTN2, TCTN3, THBD, TMEM138, TMEM216, TMEM231, TMEM237, TMEM67,TP53RK, TRAF3IP1, TRIM32, TRPC6, TTC21B, TTC8, TULP3, UMOD, VIPAS39, VPS33B,WDPCP, WDR19, WDR73, WT1, XDH, XPNPEP3, ZMYM2, ZNF423
This test aims to detect all clinically relevant variants within the coding regions of the genes evaluated. Pathogenic and likely pathogenic variants detected in these genes should be confirmed by orthogonal methods. Detected genetic variants classified as benign, likely benign, or of uncertain significance are not included in this report. Homopolymer regions and regions outside of the coding regions cannot be captured by the standard NGS target enrichment protocols. Currently, the assay does not detect large deletions and duplications. This analysis also cannot detect pathogenic variants within regions that were not analyzed (e.g.,introns, promoter and enhancer regions, long repeat regions, and mitochondrial sequence). This assay is not designed to detect mosaicism and is not designed to detect complex gene rearrangements or genomic aneuploidy events. It is important to understand that there may be variants in these genes undetectable using current technology. Additionally, there may be genes associated with hereditary kidney disease whose clinical association has not yet been definitively established. The test may therefore not detect all variants associated with hereditary kidney disease. The interpretation of variants is based on our current understanding of the genes in this panel and is based on current ACMG professional guidelines for the interpretation of germline sequence variants.Interpretations may change over time as more information about the genes in this panel becomes available. Qualified health care providers should be aware that future reclassifications of genetic variants can occur as ACMG guidelines are updated. Factors influencing the quantity and quality of extracted DNA include, but are not limited to, collection technique, the amount of buccal epithelial cells obtained, the patient’s oral hygiene, and the presence of dietary or microbial sources of nucleic acids and nucleases, as well as other interfering substances and matrix-dependent influences. PCR inhibitors, extraneous DNA, and nucleic acid-degrading enzymes may adversely affect assay results.
This laboratory-developed test (LDT) was developed, and its performance characteristics were determined by PreCheck Health Services, Inc. This test was performed at PreCheck Health Services, Inc. (CLIA ID: 10D2210020 and CAP ID:9101993), which is certified under the Clinical Laboratory ImprovementAmendments of 1988 (CLIA) as qualified to perform high complexity testing.
This assay has not been cleared or approved by the U.S. Food and Drug Administration (FDA).Clearance or approval by the FDA is not required for the clinical use of this analytically and clinically validated laboratory-developed test. This assay has been developed for clinical purposes, and it should not be regarded as investigational or for research.
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