We expect future versions of the Pathway Tools software to implement the display of subcellular localization in individual pathway in a more efficient fashion without frame duplications.
Besides those in codons 61 and 146, other KRAS exon 3 mutations represented 19% (5/26) of all KRAS changes, including one deletion (p.Ala59del), two point mutations (p.Glu49Lys and p.Gly60Val) and two large in frame duplications (p.Cys51_Ser65dup and p.Thr58_Met72dup).
However, there is no data available to determine the influence in RAS protein structure of the novel deletion (p.Ala59del) and the two novel large in frame duplications (p.Cys51_Ser65dup and p.Thr58_Met72dup) we found in exon 3, but the fact that they are located in the switch II region is an indicator that they may activate RAS by impairing GTP hydrolysis.
Quantitative fluorescent PCR analysis of genomic DNA confirmed that ISPD exons 6, 7 and 8 were homozygously duplicated in Case 9, resulting in an out-of-frame duplication (Supplementary Fig. 4) and that both her parents were carriers of the mutation (data not shown).
The genetic defect in the Tsk/+ is an in-frame duplication between exons 17 and 40 of the fibrillin-1 gene which gives rise to a large transcript and protein.
The causative 6-base in-frame duplication c.
The only other CNV present in a gene implicated in ADNSHL was an in-frame duplication of exons 18 to 20 of EYA4.
All 11 GCKR missense variants, as well as one in-frame duplication (c.17_22dup; p.R6_F7dup previously reported as p.Q8_H9insRF), were selected for comprehensive functional characterization.
This for example allowed better understanding of the genotype-phenotype correlation in a BMD patient carrying an exons 3 6 out-of-frame duplication.
One BMD patient had an out-of-frame duplication of exons 3 6 as an exception to the reading frame rule, one DMD patient showed an isolated duplication of exon 2, and one BMD patient had a deletion of exon 14.
