Table 2.

Diagnostic utility and clinical implications of genetic diagnosis in patients who completed return of results (n=41)

Age Range (yr)Clinical DiagnosisFamily HistoryGene/Genetic Diagnosis (OMIM Phenotype MIM No.)Clinical Implications
Influenced Choice of TherapyInformed PrognosisInitiated Subspecialty CareGuided Familial TestingAssisted with Donor Selection
Confirmed suspected hereditary cause (n=18)
 22–49GlomerulopathyPosNPHS1/Nephrotic syndrome type 1 (256300)YesYesNoNoNo
 22–49Tubulointerstitial diseasePosCLCN5/Dent disease (300009)NoYesNoNoYes
 ≥50GlomerulopathyNegCOL4A3/Alport syndrome, autosomal dominant/recessive; thin basement membrane disease (104200, 203780, 141200)NoNoYesNoNo
 22–49GlomerulopathyPosCOL4A4/Alport syndrome, autosomal dominant/recessive; thin basement membrane disease (104200, 203780, 141200)YesYesYesNoNo
 22–49GlomerulopathyPosCOL4A5/Alport syndrome, X-linked (301050)YesYesYesYesNo
 ≥50GlomerulopathyPosCOL4A5/Alport syndrome, X-linked (301050)NoYesYesNoNo
 ≥50GlomerulopathyPosCOL4A5/Alport syndrome, X-linked (301050)NoYesYesNoYes
 22–49GlomerulopathyPosWT1/Nephrotic syndrome type 4 (256370)YesYesNoNoNo
 22–49Congenital or cystic kidney diseaseNegEYA1/Branchio-oto-renal syndrome 1 (113650)NoYesYesYesYes
 22–49Congenital or cystic kidney diseasePosEYA1/Branchio-oto-renal syndrome 1 (113650)YesYesYesNoYes
 22–49Tubulointerstitial diseaseNegSLC12A3/Gitelman syndrome (263800)YesNoNoNoNo
 22–49Kidney failure of unknown etiologyPosMYH9/Epstein syndrome; Fechtner syndrome (153650, 153640)YesYesYesYesNo
 18–21GlomerulopathyPosINF2/FSGS 5 (613237)YesYesNoYesYes
 22–49Tubulointerstitial diseaseNegSLC5A2/renal glucosuria (233100)YesNoNoNoNo
 22–49Congenital or cystic kidney diseasePosTSC1/Tuberous sclerosis-1 (191100)aYesYesYesNoNo
 ≥50Kidney failure of unknown etiologyPosUMOD/Autosomal dominant tubulointerstitial kidney disease, UMOD-associated (609886, 162000, 603860)aNoYesNoNoNo
 22–49Tubulointerstitial diseasePosUMOD/Autosomal dominant tubulointerstitial kidney disease, UMOD-associated (609886, 162000, 603860)aNoYesNoYesYes
 22–49Tubulointerstitial diseasePosUMOD/Autosomal dominant tubulointerstitial kidney disease, UMOD-associated (609886, 162000, 603860)aYesYesNoNoYes
Identified molecular cause for undiagnosed condition (n=13)
 22–49GlomerulopathyPosCOL4A4/Alport syndrome, autosomal dominant/recessive; thin basement membrane disease (104200, 203780, 141200)NoYesYesYesNo
 22–49Kidney failure of unknown etiologyPosCOL4A5/Alport syndrome, X-linked (301050)YesYesYesNoNo
 ≥50GlomerulopathyPosCOL4A5/Alport syndrome, X-linked (301050)NoNoYesNoNo
 22–49Kidney failure of unknown etiologyPosCLCN5/Dent disease (300009)YesYesYesNoNo
 22–49Kidney failure of unknown etiologyNegPAX2/Glomerulosclerosis focal segmental 7; papillorenal syndrome (616002, 120330)NoYesYesNoNo
 ≥50Kidney failure of unknown etiologyPosTRPC6/Glomerulosclerosis focal segmental 2 (603965)NoYesNoNoNo
 22–49Kidney failure of unknown etiologyNegMC4R/Obesity, autosomal dominant (601665)YesNoYesYesNo
 22–49Kidney failure of unknown etiologyNegAPOE/Lipoprotein glomerulopathy; hyperlipoproteinemia, type 3 (611771, 617347)YesYesYesNoNo
 22–49GlomerulopathyNegCR2/FSGS 9 (616220)YesYesNoYesNo
 22–49Congenital or cystic kidney diseasePosHNF1B/Renal cysts and diabetes syndrome (137920)NoNoYesYesNo
 ≥50Tubulointerstitial diseaseNegHNF1B/Renal cysts and diabetes syndrome (137920)aYesYesYesNoNo
 22–49Kidney failure of unknown etiologyPosNPHP4/Nephronophthisis 4 (606966)NoYesYesNoNo
 22–49Tubulointerstitial diseasePosUMOD/Autosomal dominant tubulointerstitial kidney disease, UMOD-associated (609886, 162000, 603860)aNoYesNoNoNo
Reclassified disease (n=8)
 22–49GlomerulopathyPosCOL4A3/Alport syndrome, autosomal dominant/recessive; Thin basement membrane disease (104200, 203780,141200)NoYesYesYesNo
 22–49GlomerulopathyPosCOL4A4/Alport syndrome, autosomal dominant/recessive; Thin basement membrane disease (104200, 203780,141200)NoNoYesNoNo
 ≥50GlomerulopathyNegCOL4A4/Alport syndrome, autosomal dominant/recessive; Thin basement membrane disease (104200, 203780,141200)NoYesYesNoNo
 ≥50GlomerulopathyPosCOL4A4/Alport syndrome, autosomal dominant/recessive; Thin basement membrane disease (104200, 203780,141200)NoNoYesNoNo
 22–49Kidney failure of unknown etiologyPosCLCN5/Dent disease (300009)YesNoYesNoNo
 22–49Kidney failure of unknown etiologyPosCLCN5/Dent disease (300009)YesYesYesYesNo
 22–49GlomerulopathyPosSALL1/Townes–Brocks syndrome 1 (107480)NoYesYesYesYes
 ≥50GlomerulopathyPosTRPC6/Glomerulosclerosis focal segmental 2 (603965)YesNoNoNoNo
Identified a genetic variant diagnostic for an otherwise medically actionable condition (n=2)
 22–49GlomerulopathyPosSCN5A/Brugada syndrome 1; long QT syndrome 3 (601144, 603830)YesNoYesNoNo
 ≥50GlomerulopathyNegBRCA2/Hereditary breast and ovarian cancer (612555)YesNoNoYesNo
  • Diagnostic utility is grouped by rows and clinical implications by columns. Neg, Negative; Pos, Positive.

  • a Participants highlighted were crossrecruited into the eMERGE protocol (the Electronic Medical Records and Genomics Network’s Phase III Study) and underwent clinical-grade sequencing as part of their participation.