Community Consultation

Proposal SVD-WG003 (exon del/dup)

The proposal suggested to describe deletions (duplications) detected by MLPA tests (testing all exons) using the format c.(649+1_650-1)_(1331+1_1332-1)del.

The format suggested originally to describe deletions/duplications detected by MLPA tests (testing all exons) was c.650-?_1331+?del, i.e. a deletion starting in the intron preceding c.650 (first nucleotide of the first deleted exon) and ending in the intron after c.1331 (last nucleotide of the last deleted exon). However, this format is in conflict with the basic recommendation that in such cases the description should make clear what the region of uncertainty for the break point is (see Uncertainties), i.e. (position-last-normal-probe_position-first-altered-probe)_ (position-last-altered-probe_position-first-normal-probe). The Committee considered the format c.(649_650)_(1331_1332)del which is shorter but not specifically indicates that the expected break points of the change are in an intron.



To be 100% accurate one should theoretically not use the position of the introns in the description of the change but the location of the probes used in the assay (see Uncertainties). When one wants to use probe locations (e.g. with breakpoints in large exons) the suggestion is to use the central position of the probes in variant descriptions. Proposal SVD-WG003 bears in mind that:

NOTE: the description “dup” may by definition (see Duplication) only be used when the additional copy is located directly 3’-flanking the original copy (a tandem duplication). In most cases there will be no experimental proof, the method used only detects the presence of an additional copy that, in theory, can be anywhere in the genome (inserted). Discussions are ongoing how to include this uncertainty best in the description: a proposal will follow later.

Original proposal