My mutation…easily explained.

A lovely anonymous poster on the FORCE Message Boards gave a fabulous description of my gene mutation. He/she put if very simply in laymen's terms.

My mutation is EX19DEL (aka c.8332-?_8488+?del)

All these weird question marks in the mutation name are a hallmark of the HGVS (Human Genome Variation Society) naming rules for big deletions / rearrangements.

All the lab typically knows is that a certain exon (or sometimes several of them) have been moved out of its proper place.

The easiest way to think about the exons is to imagine a novel published in a magazine, a chapter in every issue. If you have a stack of magazine and want to read the whole story, you read a chapter, skip a bunch of pages after it, pick the next issue, skip some pages before the next part of the story, and read on.

If it was a gene rather than a novel, then the in-between text you skip would be called an "intervening sequence", or intron. And the chapter you read would be called an exon.

Now suppose a chapter is missing. Maybe the whole magazine issue is lost, or maybe somebody ripped out a bunch of pages. Either way you don't have the whole story. Just how many "intron" pages are missing along with it wouldn't really matter for the reader.

But the HGVS rules demand that the lab reports the exact position of the lost part, to a letter, exon and intron alike. So a report would have to say something like

c.8332-?_8488+?del

which means that the loss is from the "letter" 8332 in the story, to letter 8488, and they also miss an unknown number of "intron" letters before the "exon" chapter (that's minus-question mark), and an unknown number of letter after the exon (that's plus-question mark).

This kind of notation would typically draw a blank stare from a geneticist, of course. Are they, like, supposed to memorize where a letter 8332 is located in the story? So thankfully, the lab might explain the numeric mumbo-jumbo it in more transparent terms. Like, "it means that the exon number 19 is gone".

Mutations of this type are known as "large deletions" or "rearrangements". These "rearrangements" are not common. To make the matters worse, the traditional sequencing tests typically missed them. New, more sensitive tests have only become available recently.

Guess I was lucky. By the sounds of this, my mutuation wouldn't have been found a few years ago!