Table 2.

Diagnostic Variants Identified in Exome Sequencing

Patient Identification	Sex	Age, y	Race/E thnicit y	Clinical Presentation	Genetic Diagnosis	Gene Symbol	Sequence Variant, RSID, and ExAC Frequency	Clinical Implications of Genetic Information
Genetic diagnoses that confirmed the clinical diagnosis and their potential implications on clinical care
K008	Female	28	White	ESRD of unknown cause, has undergone kidney transplantation, son has Alport syndrome	X-linked Alport syndrome (OMIM 301050)	COL4A5	NM_000495:c.G3310T:p.G1104C†	Clarification of mode of inheritance; screening family members
							RSID: NA
							ExAC frequency: 0
K009	Male	26	White	Biopsy-proven Alport syndrome, negative FHx	X-linked Alport syndrome (OMIM 301050)	COL4A5	NM_000495:c.G2731A:p.G911R	Clarification of mode of inheritance; screening family members
							RSID: rs281874704
							ExAC frequency: 0
K024	Female	31	White	Biopsy-proven Alport syndrome, negative FHx	X-linked Alport syndrome (OMIM 301050)	COL4A5	NM_000495:c.G5042A:p.C1681Y†	Clarification of mode of inheritance; screening family members
							RSID: NA
							ExAC frequency: 0
K079	Male	22	White	Biopsy-proven Alport syndrome, positive FHx	X-linked Alport syndrome (OMIM 301050)	COL4A5	NM_000495:c.G2474A:p.G825E†	Clarification of mode of inheritance; screening family members
							RSID: NA
							ExAC frequency: 0
K054	Female	31	White	Nail–patella syndrome with biopsy-proven FSGS	Nail–patella syndrome (OMIM 161200)	LMX1B	NM_001174146: 775_776del: p.S259Cfs*38	Do not consider immunosuppression; refer for transplant
							RSID: NA
							ExAC frequency: 0
K015	Male	37	Asian	Fabry disease by biopsy and enzyme activity, ESRD	Fabry disease(OMIM 301500)	GLA	NM_000169:c.A886G:p.M296V	Screening family members; continue enzyme therapy
							RSID: rs104894830
							ExAC frequency: 4 × 10−6
Genetic diagnoses that provided new information and their potential implications on clinical care
K030	Male	19	African American	CKD of unknown cause with bilateral renal hypoplasia, hypogonadism; history of repaired atrial septal defect; offspring of healthy parents	CHARGE syndrome (OMIM 214800)	CHD7	NM_017780:c.G8554A:p.D2852N†	Screening for hearing and visual loss, cranial nerve dysfunction, and learning disability; caution during anesthesia because of upper airway maldevelopment
							RSID: NA
							ExAC frequency: 0
KGY1	Male	35	White	Familial proteinuric CKD of unknown cause, inconclusive results on biopsies at age 6 and 12 y, brother with proteinuria (never had biopsy)	Dent disease 1 (OMIM 300009)	CLCN5	NM_000084:c.2057delG:p.S686Tfs*5	Therapy with thiazide diuretics and citrates; no posttransplant recurrence expected; brother screened and diagnosed with Dent disease 1
							RSID: NA
							ExAC frequency: 0
K014	Female	22	White	ESRD of unknown cause, has undergone kidney transplantation, positive FHx of microhematuria on father’s side	Autosomal recessive Alport syndrome (OMIM 203780)	COL4A3	NM_000091:c.G1558C:p.G520R RSID: NA ExAC frequency: 0	Posttransplant recurrence unlikely; compound heterozygosity confirmed by testing allele transmission in offspring; immunosuppressive therapy not indicated; family counseling
							NM_000091:c.T4421C:p.L1474P RSID: rs200302125 ExAC frequency: 0.003
K078	Female	28	White	FSGS by biopsy, has had kidney transplantation, sibling died at age 17 y with anasarca, FHx of hematuria	Autosomal recessive Alport syndrome (OMIM 203780)	COL4A4	NM_000092:c.G4288A:p.G1430R RSID: NA ExAC frequency: 2.3 × 10−3	Compound heterozygosity confirmed by testing allele transmission in offspring; immunosuppressive therapy not indicated; family counseling; patient opted to pursue pregnancy after genetic diagnosis clarified recessive inheritance
							NM_000092:c.213_239del:p.P72_G80delPQGPIGPLG RSID: NA ExAC frequency: 2.3 × 10−3
K058	Male	28	White	FSGS by biopsy, undergoing kidney transplant evaluation positive FHx for nephropathy	Autosomal dominant Alport syndrome (OMIM 104200)	COL4A4	NM_000092:c.G1145C:p.G382A†	Immunosuppressive therapy not indicated; family screening for donor evaluation; referred for gene therapy trial
							RSID: rs751952236
							ExAC frequency: 4 × 10−5
K028	Female	57	White	mild CKD of unknown cause with hematuria. TBMD diagnosed as a child (self-reported),	X-linked Alport syndrome (OMIM 301050)	COL4A5	NM_000495:c.G5030A:p.R1677Q	Auditory and ophthalmology screening; referred for clinical trial (NCT02855268)
							RSID: rs104886308
							ExAC frequency: 2.3 × 10−5
K064	Male	48	White	CKD of unknown cause with congenital small left kidney, diabetes, no prior kidney biopsy.	HNF1B-associated disease‡ (OMIM 137920)	HNF1B	NM_000458:c.C742T:p.Q248X	Insulin therapy; screening for hyperuricemia, hypomagnesemia, and hypoparathyroidism; family screening and counseling
							RSID: NA
							ExAC frequency: 0
K065	Male	20	White	Presented with hypertension and hypokalemia at age 13 y	Liddle syndrome (OMIM 177200)	SCNN1G	NM_001039:c.C1874G:p.P625R†	Treat with amiloride
							RSID: NA
							ExAC frequency: 0
K027	Female	44	White	Gitelman syndrome, type 2 diabetes	Gitelman syndrome (OMIM 263800)	SLC12A3	NM_000339: A2899G:p.R967G RSID: NA ExAC frequency: 0	–
							NM_000339:c.2986_2987insGCTC:p.Y999Afs*50 RSID: NA ExAC frequency: 0
K006	Female	42	White	Biopsy-proven FSGS, mother with ESRD has undergone kidney transplantation	FSGS type 2(OMIM 603965)	TRPC6	TRPC6:NM_004621: A434G:p.H145R†	Affected mother tested positive for mutation; immunosuppression is not indicated
							RSID: NA
							ExAC frequency: 0
K007	Male	55	White	CKD with chronic tubulointerstitial nephropathy on biopsy, undergoing kidney transplant evaluation, Strong FHx for dominant transmission of CKD/ESRD	Autosomal dominant medullary cystic kidney disease type 2(OMIM 603860)	UMOD	NM_001008389:c.G317A:p.C106F†	Family screening and counseling; monitor uric acid levels
							RSID: rs398123697
							ExAC frequency: 3.7 × 10−5
K016	Male	21	White/Hispanic	Gout and CKD of unknown cause, no biopsy; positive FHx for dominant transmission of ESRD/gout	Autosomal dominant medullary cystic kidney disease type 2 (OMIM 603860)	UMOD	NM_001008389:c.G774C:p.W258C†	Family screening and counseling; monitor uric acid levels
							RSID: NA
							ExAC frequency: 0
K043	Female	45	Asian	CKD with chronic tubulointerstitial nephropathy by biopsy, positive FHx for dominant transmission of CKD and gout	Autosomal dominant medullary cystic kidney disease type 2 (OMIM 603860)	UMOD	NM_001008389:c.T638A:p.M213K†	Family screening and counseling; monitor uric acid levels
							RSID: NA
							ExAC frequency: 0

CHARGE = coloboma, heart defects, atresia choanae, growth retardation, genital abnormalities, and ear abnormalities; CKD = chronic kidney disease; ESRD = end-stage renal disease; ExAC = Exome Aggregation Consortium; FHx = family history; FSGS = focal segmental glomerulosclerosis; NA = not applicable ; OMIM = Online Mendelian Inheritance in Man; RSID = Reference Single Nucleotide Polymorphism identification number ; TBMD = thin basement membrane disease.

^†Likely a pathogenic mutation.

^‡Also known as renal cysts and diabetes syndrome or maturity-onset diabetes of the young type 5.