Table 2:
Details of ADPKD pathologic and possibly modifying variants.
| Pedigree | Gene | Ex/IVS | Protein variant | cDNA variant | Mutation type | Functional effect | Mayo Clinic designation | gnomAD1 | ADPKD Variant Database | dbSNP ID |
|---|---|---|---|---|---|---|---|---|---|---|
| Pathogenic variants | ||||||||||
| 1 | PKD1 | 5′UTR-Ex14 | p.Met1fs | c.(1-2kb)_(3295)del23.5kb | Large deletion | Truncating | DP | No | ||
| 2 | PKD1-TSC2 | 2–46 and 18–41 |
PKD1: p.Leu72fs* TSC2: p.Ala1614fs* |
Chr16: (2.121Mb)_(2.170Mb)del48.3kb-PKD1: c.(216)_(12909*)del30.9kb TSC2: c.(1840)_(5352)del17.4kb |
Large deletion | Truncating | DP | No | ||
| 3 | PKD1 | 5 | p.Glu226* | c.676G>T | Nonsense | Truncating | DP | No | ||
| 4 | PKD1 | 15 | p.Met1219fs | c.3656_6911del3256 | Large deletion | Truncating | DP | No | ||
| 5 | PKD1 | 15 | p.Arg1672fs | c.5014_5015delAG | Frameshift | Truncating | DP | Yes | rs1555455457 | |
| 6 | PKD1 | 15 | p.Gln2058Pro | c.6173A>C | Missense | Non-truncating | LP | 0 | No | |
| 7 | PKD1 | 15 | p.Arg2163* | c.6487C>T | Nonsense | Truncating | DP | Yes | ||
| 8 | PKD1 | 15 | p.Arg2220_Pro2224del5 | c.6657_6671del15 | InFrame D/I | Non-truncating | DP | Yes | ||
| 9 | PKD1 | 15 | p.Gln2243* | c.6727C>T | Nonsense | Truncating | DP | Yes | rs1567191609 | |
| 10 | PKD1 | 15 | p.Gly2278Arg | c.6832G>A | Missense | Non-truncating | LP | 0 | Yes | rs1555454145 |
| 11 | PKD1 | 15 | p.Trp2298Arg | c.6892T>G | Missense | Non-truncating | HLP | 0 | No | |
| 12 | PKD1 | IVS15 | p.Arg2306fs | c.6916-9G>A | Splice | Non-truncating | LP | 0 | Yes | |
| 13 | PKD1 | 17 | p.Cys2373* | c.7119C>A | Nonsense | Truncating | DP | Yes | ||
| 14 | PKD1 | 17 | p.Arg2404fs | c.7197_7209dup13 | Frameshift | Truncating | DP | No | ||
| 15 | PKD1 | 23 | p.Phe2806Ser | c.8417T>C | Missense | Non-truncating | LP | 0 | No | |
| 16 | PKD1 | IVS24 | p.Gly2983fs | c.8948+2dupT | Splice | Non-truncating | LP | No | ||
| 17 | PKD1 | 25 | p.Glu3020* | c.9058G>T | Nonsense | Truncating | DP | Yes | ||
| 18 | PKD1 | 25 | p.Leu3010Gln | c.9029T>A | Missense | Non-truncating | LP | 0 | No | rs750501225 |
| 19 | PKD1 | 26 | p.Pro3069fs | c.9205_9224del20insGACA | Frameshift | Truncating | DP | No | ||
| 20 | PKD1 | 36 | p.Ser3593Arg | c.10779C>G | Missense | Non-truncating | LP | 0 | No | |
| 21 | PKD1 | 39 | p.Tyr3734* | c.11202C>A | Nonsense | Truncating | DP | No | [54] | |
| 22 | PKD1 | 40 | p.Tyr3759fs | c.11274_11275delCT | Frameshift | Truncating | DP | No | rs1555446105 | |
| 23 | PKD1 | 40 | p.Asp3780_Asp3782del3 | c.11339_11347del9 | InFrame D/I | Non-truncating | HLP | No | ||
| 24 | PKD1 | 41 | p.Trp3842Arg | c.11524T>C | Missense | Non-truncating | HLP | 0x | Yes | rs1057518959 |
| 25 | PKD1 | IVS42-3′UTR | p.Val3905fs | c.11712+55_12909974del2.6kb | Large deletion | Truncating | DP | No | ||
| 26 | PKD1 | 43 | p.Gln3955fs | c.11863dupC | Frameshift | Truncating | DP | No | [43] | |
| 27 | PKD1 | 44 | p.Gln4005* | c.12013C>T | Nonsense | Truncating | DP | Yes | rs1567148587 | |
| 28 | PKD1 | 46 | p.Phe4219fs | c.12627_12655dup29 | Frameshift | Truncating | DP | No | ||
| 29 | IFT140 | 14 | p.Gly509? | c.1525-1G>A | Splice | Truncating | DP | NA | [16] | |
| Other possible relevant variants | ||||||||||
| 22 | PKD1 | 8 | p.Thr558Met | c.1673C>T | Missense | Non-truncating | LN | 8x | No | rs781572938 |
| Unsolved# | PKD1 | 15 | p.Arg1549Gln | 4646G>A | Missense | Non-truncating | LN | 2x | No | rs530555146 |
| 9 | PKD1 | 15 | p.His1769Tyr | c.5305C>T | Missense | Non-truncating | Mod | 5x | No | |
| Unsolved | PKD1 | 23 | p.Thr2756Ile | c.8267C>T | Missense | Non-truncating | VUS | 49x | No | rs141296093 |
| 22 | PKD1 | 27 | p.Arg3169Trp | c.9505C>T | Missense | Non-truncating | LN | 8x | No | rs765180455 |
| 21 | PKD1 | 36 | p.Lys3607Met | c.10820A>T | Missense | Non-truncating | VUS | 0x | No | |
| 4 | PKD2 | 15 | p.Met905Leu | c.2713A>C | Splice | Non-truncating | VUS | 77x | 2 | rs573871626 |
| Unsolved | IFT122 | 30 | p.Leu1257_Pro1263del | c.3769_3789+5del26 | Frameshift | Truncating | DP (rec) | 0x | No | |
| Unsolveda | COL4A1 | 30 | p.Pro739Leu | c.2216C>T | Missense | Non-truncating | VUS | 13x | No | |
aCo-inherited by the same patient.
dbSNP: Single Nucleotide Polymorphism Database; FS del: frameshift deletion; FS dup: frameshift duplication; IF del: in-frame deletion; DP: definitely pathogenic; LP: likely pathogenic; VUS: variant of uncertain significance; LN: likely neutral; Rec: recessive; HLP: highly likely pathogenic; Mod: moderate; Ex: exon; IVS: intervening sequence.