Table 2.
Pathogenic variants in COL4A genes
| Patient ID (Family ID) | Sex | Ethnicity | Age at Disease Onset | Age at ESKD | Exon Number | Nucleotide Change | Protein Effect | Allele Frequency | Zygosity | References |
|---|---|---|---|---|---|---|---|---|---|---|
| Pathogenic COL4A3 variants | ||||||||||
| 7215 (F23) | F | EUR | Early teens | n/a (34) | 31 | c.2452G>A | Gly818Arg | 1.17E-05 | Het | S17, S18 |
| 2555 (s) | F | EUR | 36 | 48 | 42 | c.3655G>T | Gly1219Cys | 0 | Het | S19 |
| 6062 (s) | F | EUR | 30 | unknown | 21 | c.1219G>C | Gly407Arg | 0 | Het | S20 |
| Pathogenic COL4A4 variants | ||||||||||
| 6329 (F14) | M | EUR | 42 | n/a (48) | 32 | c.2906C>G | Ser969stop | 6.49E-05 | Het | S18, S21–S24 |
| Pathogenic COL4A5 variants | ||||||||||
| 5515 (F8) | M | EUR | 32 | n/a (42) | 50 | c.4946T>G | Leu1649Arg | 0 | Hemi | S25 |
| 5519 (F8) | M | EUR | 25 | n/a (44) | 50 | c.4946T>G | Leu1649Arg | 0 | Hemi | S25 |
| 2594 (F16) | F | EUR | 28 | 40 | 20 | c.1276G>A | Gly426Arg | 0 | Het | S26, S27 |
| 1590 (s) | F | EUR | 28 | n/a (56) | 35 | c.3017G>T | Gly1006Val | 0 | Het | S28 |
| 2480 (s) | F | Admixed | Unk | 30 | 33 | c.2804G>A | Gly935Asp | 0 | Het | S27 |
| 4976 (s) | M | EUR | 41 | n/a (56) | 25 | c.1781G>A | Gly594Asp | 0 | Hemi | S29 |
| 6223 (s) | F | EUR | Unk | unknown | 31 | c.2605G>A | Gly869Arg | 0 | Het | S26, S30–S35 |
| 5269 (s) | M | EUR | 57 | 66 | 39 | c.3508G>A | Gly1170Ser | 0 | Hemi | S17, S36–S39 |
The following minor allele frequency (MAF) cut-offs as determined in gnomAD (http://gnomad.broadinstitute.org/) were used for dominant and recessive disease genes respectively: 0.00005 and 0.005 (accessed February 22, 2018). The MAF of the only COL4A4 variant exceeds the cut-off, but it is a well established founder mutation. Patients 5515 and 5519 are brothers. (F) designates family pedigree number whereas (s) indicates a sporadic case. Het indicates heterozygous and hemi indicates hemizygous. All references refer to the supplemental reference list, which can be found in the Supplemental Material, and indicate previous reports of the variant. Age at ESKD was indicated as n/a for patients without ESKD, followed by their age at time of analysis in parentheses.. F, female; EUR, European; M, male.