Table 1 Overview of identified variants.

From: Identification of disease-causing variants by comprehensive genetic testing with exome sequencing in adults with suspicion of hereditary FSGS

Family (origin)

Gene (NM_number)

Chromosomal position (hg19)

Nucleotide change, amino acid change, and corresponding ClinVar and/or LOVD ID

Inheritance

gnomADa MAF

ACMG ratingb

Biopsy (initial clinical presentation)

Affected (gender)

Positive familial history

Consanguinity

Individual ages (years)

CKD-stage (age in years)

Present inclusion criteriac

Previously published

           

Disease onset

ESRD

   

F9 (GE)

COL4A3 (NM_000091.4)

NC_000002.11: g.[228144508G>C]; [228172594T>C]

c.[2126-1G>C];[4421T>C], p.[?];[Leu1474Pro] LOVD ID: 0000665278; ClinVar ID: SCV001149720.1

AR

Not listed; 2.66e−3

PVS1/PM2, PS4 (moderate, in trans with pathogenic variant)/ PM1/PM3/PP3

FSGS (NS)

1 (m)

No

No

26

–

G3aA3 (30)

1

No; [42, 43]

F274 (GE)

COL4A5 (NM_000495.3)

NC_000023.10: g.[107850086G>A]; [=]

c.[2359G>A];[=], p.[Gly787Arg];[=] ClinVar ID: SCV001150068.1

XL

Not listed

PS2/PM1 (strong)/PM2/PM5/PP3

Focal segmental and global GS (hypertension)

1 (f)

No

No

32.5

–

G3aA3 (40)

1, 3

No

F26 (TU)

COQ8B (NM_024876.4)

NC_000019.9: g.[41198128C>A]; [41198128C>A]

c.1447G>T(;)(1447G>T), p.Glu483*(;)(Glu483*) ClinVar ID: SCV001149996.1

AR

5.16e−5 (no homozygotes present)

PVS1/PS4 (moderate)/ PM2

FSGS (proteinuria)

2 (m, f)

Yes

Yes

24, 32

24, –

G5-D (24), G2A3 (32)

1, 5, 6

[38]

F103 (GE)

INF2 (NM_022489.3)

NC_000014.8: g.[105169540G>C]; [=]

c.[490G>C];[=], p.[Ala164Pro];[=] LOVD ID: 0000665276

AD

Not listed

PM1/PM2/PP1 (strong)/PP3/

Minimal change disease, mesangioprol. GN IgA type (proteinuria, hypertension)

10 (m, m, f, f, f, m, m, m, m, m)

Yes

No

18, 19, 24, 25, 18, 32, 32, 19, 31, 26

30, 39, –, –, 38, 38, –, –, –, –

G5-D (30), G5-D (39), G1A? (39), G2A? (35), G5-D (38), G5-D (38), n.k., G4A3 (38), G3bA3 (32), G2A3 (27)

1, 2, 5

[44]

F27 (GE)

INF2 (NM_022489.3)

NC_000014.8: g.[105169653C>T]; [=]

c.[529C>T];[=], p.[Arg177Cys];[=] ClinVar ID: SCV001149810.1

AD

Not listed

PS4 (moderate)/PM1/PM2/PP3

IgA/Immune complex nephritis, FSGSd (proteinuria)

1 (m)

No

No

18

–

G4A3 (37)

2

[45]

F332 (GE)

MUC1 (NM_001204285.1)

NC_0000001.10: g.(155160963_155162030)insC

c.(103_564)insG;[=], p.[?];[=] LOVD ID: 0000673664

AD

Not listed

PS3/PS4 (moderate)/PM2

Focal global GS (creatinine increase)

1 (m)

Yes

No

32

41

G5-D (41)

1, 5

[26]

F520 (RO)

WT1 (NM_024426.4)

NC_000011.9: g.[32413514G>A]; [=]

c.[1432+4C>T];[=], p.[?];[=] LOVD ID: 0000673826

AD

Not listed

PS3/PS4 (moderate)/PM2/PP3

FSGS (edema)

1 (m [f])e

No

No

18

18

G5-D (18)

1, 2, 4

[46]

  1. P pathogenic, PP pathogenic supporting, VS very strong, S strong, M moderate, A? albuminuria unknown, AR autosomal recessive, AD autosomal dominant, ClinVar ID https://www.ncbi.nlm.nih.gov/clinvar/, CKD V-D chronic kidney disease stadium V-dialysis, XL X-linked, ESRD end-stage renal disease, FSGS focal segmental glomerulosclerosis, GE Germany, LOVD ID https://databases.lovd.nl/shared, MAF minor allele frequency, NS nephrotic syndrome, n.k. not known, – not applicable, RO Romania, TU Turkey.
  2. aGenome Aggregation Database (https://gnomad.broadinstitute.org/).
  3. bSee [24, 25].
  4. cInclusion criteria: 1: absence of a secondary cause for FSGS; 2: age ≤ 25 years at initial manifestation; 3: kidney biopsy with suspicion of a hereditary cause; 4: extrarenal manifestation; 5: positive familial history; and 6: reported consanguinity.
  5. dInitial biopsy IgA/immunocomplex nephritis, second biopsy 7 years later FSGS.
  6. eGenetic sex is a male karyotype (46,XY), the phenotype is female with unfulfilled desire to have children.
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