Table IIC.

Classification of probable pathogenic mutations: Small deletions

Mutation DesignationConservation OrthologslProtein Domain ConservationdSegregation AnalysisfOther DescriptiongOther Indeterminate VarianthVariant ScoreiMutation Groupj
PKD1
    910delDVVCPKDII (C)F2NovelN14B
    F1992L; T1993delCPKDXV (C)N/A1XkN13B
    F2979delIN/DN/A1XkN13B
    F3168delIPLAT (I)N/ANovelN15B
    L3287delITM (HC)N/ANovelN14B
PKD2
    S378delHCN/DN/ANovelY7C
    R878delIN/DN/ANovelY7C
  • a GD, Grantham distance; GV, Grantham variation; MG, mutation group; RT-PCR, reverse transcription–PCR.

  • b Score of chemical difference between the normal and mutated residue (high score, greater difference).

  • c Score of chemical difference between orthologs (human, mouse, rat, dog, chicken, frog, and fish [fi]; 0 = completed conserved). Residue and species shown if GV>GD.

  • d Domain containing residue (see Concise Methods for details): WSC, PKD repeats, REJ, GPS, PLAT; TM, transmembrane region; PC, polycystin motif A or B; GPB, G-protein binding region; ERL, ER localization signal51; N/D, no domain defined. Level of conservation: I, invariant; HC, highly conserved (>80%); C, conserved (80 to 50%); NC, not conserved (<50%); DSS, predicted to disrupt secondary structure.

  • e ND, novel donor; NA, novel acceptor; LD, loss of donor; LA, loss of acceptor; N/P, none predicted; 0.1 to 1, weakly to strongly predicted splice site.

  • f Segregation demonstrated in: S, sibs #; F, family # (at least two generations); N/A, samples not available; FP, segregation in family in previous description.

  • g Previous description of variant as mutation (#X ref.) or recurrence within study (#X); or substitution of same residue.

  • h Other indeterminate variant found associated with probable mutation: Y, yes (see Table I for details); N, no.

  • i Variant score: >11, MG = B; 5 to 10, MG = C. Atypical splicing changes proven by RT-PCR, MG = A.

  • j A, definite; B, highly likely; C, likely.

  • k Details of previous descriptions in HGMD and/or PKDB.

  • l I, invariant; HC, highly conserved (>80%); C, conserved (80 to 50%).

  • m Loss of positive residue after TM.

  • n Abnormal splicing demonstrated by RT-PCR: Y, yes; N/A, sample not available.

  • o Not predicted by Splice Site Prediction Neural Network.