Table 2.
Summary of somatic mutations in PKD genes by cyst for nine patients
| Patienta/Gene | Cyst | Constitutional Mutation | Exon | Somatic Mutation | Exon/Intron | Mutation Type | Mutation Designation |
|---|---|---|---|---|---|---|---|
| BS9001424/PKD1 | L1 | c.4745 G>C, p.Trp1582Ser (CADD=26.3) | Exon 15 | ND | |||
| L2 | c.4798dup, p.Thr1600Asnfs*15 | Exon 15 | Frameshift | Pathogenic | |||
| L3 | c.12216_12217del, p.Thr4073Profs*83 | Exon 45 | Frameshift | Pathogenic | |||
| L4 | c.348_352del, p.Asn116Lysfs*2 | Exon 3 | Frameshift | Pathogenic | |||
| L5 | c.3225del, p.Pro1076Argfs*28 | Exon14 | Frameshift | Pathogenic | |||
| L6 | c.348_352del, p.Asn116Lysfs*2 | Exon 3 | Frameshift | Pathogenic | |||
| R1 | c.11888G>A, p.Trp3963* | Exon 43 | Nonsense | Pathogenic | |||
| R2 | c.5395C>T, p.Gln1799* | Exon 15 | Nonsense | Pathogenic | |||
| R4 | c.3162–2A>C | IVS 11 | Splicing | Pathogenic | |||
| R5 | c.4745 G>C,p.Trp1582Ser (LOH) | Exon 15 | LOH | Likely pathogenic | |||
| PJ9001456/PKD1 | L1 | c.6364delG, p.Val2122Lysfs*3 | Exon 15 | ND | |||
| L4 | c.6364delG, p.Val2122Lysfs*3(LOH) | Exon 15 | LOH | Pathogenic | |||
| L5 | c.348_352del, p.Asn116Lysfs*2 | Exon 3 | Frameshift | Pathogenic | |||
| L6 | c.8016+1del | Exon 21 | Splicing | Pathogenic | |||
| L7 | c.12006_12010del, p.Gln4004Alafs*151 | Exon 44 | Frameshift | Pathogenic | |||
| L10 | c.7655_7658 delinsTTG, p.Ala2552Valfs*68 | Exon 19 | Frameshift | Pathogenic | |||
| L11 | c.3745del, p.Asp1249Thrfs*24 | Exon 15 | Frameshift | Pathogenic | |||
| L12 | c.6364delG, p.Val2122Lysfs*3(LOH) | Exon 15 | LOH | Pathogenic | |||
| L15 | c.1284_1292del, p.Trp429_Gln431del | Exon 6 | In-frame deletion | Likely pathogenic | |||
| R4 | c.3831_3847del, p.Ser1278Glyfs*17 | Exon 15 | Frameshift | Pathogenic | |||
| R7 | c.12004–2_12019del (splice_acceptor) | Exon 44 | Splicing | Pathogenic | |||
| R16 | ND | ||||||
| DR9001565/PKD1 | L3 | c.9504C>G, p.Phe3168Leu (CADD=27) | Exon 27 | c.9504C>G,p.Phe3168Leu (LOH) | Exon 27 | LOH | Pathogenic |
| L5 | c.8935_8937delTTC, p.Phe2979del | Exon 24 | In-frame deletion | Likely pathogenic | |||
| L7 | c.5395C>T, p.Gln1799* | Exon 15 | Nonsense | Pathogenic | |||
| R8 | c.2157del, p.His719Glnfs*66 | Exon 11 | Frameshift | Pathogenic | |||
| R9 | c.1789del, p.Gln597Argfs*188 | Exon 9 | Frameshift | Pathogenic | |||
| c.4916dup, p.Gly1640Argfs*18 | Exon 15 | Frameshift | Pathogenic | ||||
| R10 | c.5180del, p.Pro1727Argfs*32 | Exon 15 | Frameshift | Pathogenic | |||
| R13 | c.12711C>A, p.Tyr4237* | Exon 46 | Nonsense | Pathogenic | |||
| CDS001574/PKD1 | L2 | c.10084del, p.Gln3362Serfs*35 | Exon 31 | c.10314_10315insGCTGGCA, p.Arg3439Alafs*34 | Exon 33b | Frameshift | Pathogenic |
| L9 | c.348_352del, p.Asn116Lysfs*2 | Exon 3 | Frameshift | Pathogenic | |||
| R6 | c.11817G>A, p.Trp3939* | Exon 43 | Nonsense | Pathogenic | |||
| R9 | c.11884_11912del, p.Gln3962Alafs*5 | Exon 43 | Frameshift | Pathogenic | |||
| R10 | c.10084del, p.Gln3362Serfs*35 (LOH) | Exon 31 | LOH | Pathogenic | |||
| BJA001578/PKD1 | L3 | c.3929_3930del, p.Asp1310Glyfs*120 | Exon 43 | c.6558_6568del, p.Trp2187Serfs*71 | Exon 15 | Frameshift | Pathogenic |
| L4 | c.10948delC, p.His3650Thrfs*34 | Exon 37 | Frameshift | Pathogenic | |||
| L8 | c.10319del, p.Gly3440Alafs*33/CNV* | Exon 33 | Frameshift | Pathogenic | |||
| R2 | ND | ||||||
| R4 | c.1551_1560dup, p.Leu521* | Exon 7 | Frameshift | Pathogenic | |||
| R10 | c.412C>T, p.Arg138* | Exon 4 | Nonsense | Pathogenic | |||
| R11 | c.3929_3930del, p.Asp1310Glyfs*120 (LOH) | Exon 45 | LOH | Pathogenic | |||
| R13 | ND | ||||||
| R16 | c.12707T>A, p.Val4236Asp | Exon 46 | Missense | Likely pathogenic | |||
| (CADD=21.4) | |||||||
| CMJ001593/PKD1 | L2 | c.10406_10407insG, p.Asp3469Glufs*2 | Exon 34 | c.6994_7000dup, p.Val2334Glyfs*88 | Exon 16 | Frameshift | Pathogenic |
| L3 | c.6384C>A, p.Asn2128Lys | Exon 15 | Missense | Likely pathogenic | |||
| (CADD=26.7) | |||||||
| L10 | c.10977del, p.Glu3660Lysfs*24 | Exon 37 | Frameshift | Pathogenic | |||
| L11 | c.8815G>T, p.Glu2939* | Exon 24 | Nonsense | Pathogenic | |||
| R3 | c.11817G>A, p.Trp3939* | Exon 43 | Nonsense | Pathogenic | |||
| R9 | c.11817G>A, p.Trp3939* | Exon 43 | Nonsense | Pathogenic | |||
| RP9001591/PKD1 | L2 | c.G10549T, p.Glu3517* | Exon 35 | c.8996_8997insG, p.Phe2999Leufs*70 | Exon 25 | Frameshift | Pathogenic |
| L11 | c.G10549T, p.Glu3517* (LOH) | Exon 35 | LOH | Pathogenic | |||
| R17 | c.1005delC, p.Val336Cysfs*129 | Exon 5 | Frameshift | Pathogenic | |||
| JS9001595/PKD1 | R2 | c.6743_6744dup, p.Val2249Metfs*2 | Exon 15 | c.10220+2T>G | IVS 35 | Splicing | Pathogenic |
| R10 | c.3184C>T, p.Gln1062* | Exon 14 | Nonsense | Pathogenic | |||
| BH9002280/PKD2 | L1 | c.923del, p.Phe308Serfs*9 | Exon 4 | c.2409delA, p.Ser804Valfs*40 | Exon 13 | Frameshift | Pathogenic |
| L2 | c.242 C>A, p.Ser81* | Exon 1 | Nonsense | Pathogenic | |||
| L5 | c.962 T>A, p.Ile321Lys (CADD=24.6) | Exon 4 | Missense | Likely pathogenic | |||
| L6 | c.1843G>A, p.Ala615Thr (CADD=33.0) | Exon 8 | Missense | Likely pathogenic | |||
| L9 | c.1258A>T, p.Arg420Trp (CADD=27.7) | Exon 5 | Missense | Likely pathogenic | |||
| R1 | ND | ||||||
| R2 | c.1392A>G, p.=c | Exon 6 | Splicing | Likely pathogenic | |||
| R7 | c.1366 C>T, p.Gln456* | Exon 6 | Nonsense | Pathogenic | |||
| R8 | c.2682del, p.Gly895Valfs*14 | Exon 15 | Frameshift | Pathogenic |
ND, mutation not detected; L, Left kidney; R, Right kidney. LOH. loss of heterozygosity.
a
Probable pathogenic mutation as evaluated by CADD. A CADD value of ≥15 suggests the variant is likely pathogenic (http://cadd.gs.washington.edu/).
b
PKD1 exon 33 single-copy region.
c
Mutation (c.1392A>G, p.=) predicted to create a new donor splice site using splice site prediction tools (ESEfinder3.0, NNSplice and Human splicing finder3.1) with default settings.