When Genetic Changes Occur


Your child’s genetic lab results should list their type of mutation, also referred to as an Alteration.
When an alteration to your child’s genetic sequence is identified, this is called a “mutation.” They may also be called: alterations, variations, variants or chromosomal rearrangements.

In the summary text on your child’s lab report, there may be more information about the finding. Most laboratories will list the evidence used to classify the finding as harmful, or “disease-causing.” A laboratory report may also give you information about the type of mutation that was identified.


The genetic lab results of your child should list their type of mutation, also called alteration. When a change in your child's genetic sequence is identified, we are talking about "mutation". In the summary of your child's lab report, there may be information about the type of mutation identified.





Frameshift Mutations - occur when the addition or loss of DNA causes a shift in the genetic code and changes the types of amino acids created. Insertions, deletions and duplications can all be frame shift mutations; it depends on the size of the deleted or duplicated material.
Duplication - a piece of DNA is copied one or more times.
Deletion - a piece of DNA is removed. The deletions may be large or small and the gene function may not be modified, depending on the location of the missing piece.
Insertion - a piece of DNA is inserted, modifying the original genetic code.
Missense - One amino acid is substituted for another, which changes the function of the protein. The missense mutations may be the most difficult to interpret for a laboratory because, while some changes in missense may be harmful, they do not affect the operation of SYNGAP1 at all. Missense mutations can significantly alter the function of the SYNGAP1 gene, slightly or not at all.
Nonsense - Instead of substituting one amino acid for another, as in the case of a missense mutation, the code stops prematurely, resulting in an incomplete protein.




Report content:

DNA is composed of 4 chemical building blocks - adenine, thymine, cytosine and guanine - A, T, C and G.

In a section called "Nucleotide Change" or "cDNA" in the lab report, you may see something like this (for a missense):


This indicates the nucleotide change that has taken place. On nucleotide number 2583, a C (cyosine) has been replaced by an T (thymine).

You can also see something like this on the 1st page of a section called "Protein Change" or "Variation":


This code indicates the protein change. In this case, nucleotide change c.2583C>T resulted in the replacement of arginine (Arg) in amino acid position 861 by a histidine (His). Arginine and histidine are two types of amino acids.

Most lab reports will show both changes in DNA ("nucleic acid") and proteins ("amino acid"). These can be used interchangeably.


What is an exon?

A gene is like a book and it contains chapters. Chapters (exons) are separated by cover pages (introns).
Syngap1 gene definition found in DNA is composed of 19 chapters (19 exons). These are the information used to create the Syngap1 protein which is then later used by the brain. Introns are not used to code protein but are still an important piece of the gene.

When a mutation occurs, it can be in one of the 19 exons. As the exons do have not all the same size (think about a number of chapter pages in a book) then some bigger chapter are more subject to mutation statistically. 
The biggest exons are the exon 8 and exon 15 which cover more than 40% of gene definition. The 60% remaining are spread across the other 17 exons (with between 2% and 6% mutation chances each). 

Mutation in introns exists as well. Most of the time, this does not impact protein creation but in rare cases, this impact the exon reading when creating the protein. We can see that like a chapter cover page misinformation which will impact the book reading even if chapter content is correct.

Location of the mutation does not give yet a clear picture of severity or drug efficiency.


If you do want to know on which exon the mutation is located (if not specified in your genetic report) then the table below can be used. You need to look at the first number found in genetic test after the "p." example: p.Lys277Glnfs*7 will be on exon 8. (look at 277)

1 - 1-23
2 - 23-63
3 - 64-99
4 - 99-129
5 - 130-170
6 - 170-221
7 - 222-254
8 - 255-462
9 - 463-511
10 - 511-559
11 - 559-638
12 - 638-705
13 - 706-765
14 - 765-779
15 - 779-1136
16 - 1137-1194
17 - 1195-1265
18 - 1265-1295
19 - 1296-1343

This number defines the location of the amino acid where the mutation start. If your genetic report has no "p." then use the value found in "c." and divide it by 3 to find the exon in the table above. 

Syngap1 gene is composed of 1343 amino acid (when we count only the exons). Each amino acid is created by a combination of 3 nucleotides (a, t, g, c). This means that a single nucleotide/letter error in a text of 4029 characters (3x1343=4029) can lead to Syngap1 spectrum syndrome... This is really a minimal "bad luck event" knowing that the whole DNA has around 3 billions nucleotides...

Other important terms you may see on your reports:

Autosomal Dominant – indicates that an individual has a 50% chance of passing down the mutation to any offspring
De Novo – the mutation is present for the first time and was not inherited from either parent.
Heterozygous – having dissimilar pairs of genes
Allele – alternative form of a gene that arises from mutation
Codon – a sequence of three nucleotides together that form a unit of genetic code in a DNA or RNA molecule



Disclaimer: The information provided on this website is to inform and help parents cope with the sudden, unexpected change in their life due to a SYNGAP1 diagnosis. The information contained on this site is not intended to replace information you have received from doctors or other health professionals.
We are not doctors, we are parents of children diagnosed with a SYNGAP1 change.