Which of the following is likely to identify multiple copies of TPSAB1 (at this point of medical progress in February 2025)? I've spoken to HATS researchers, and this is a summary of the current status.

1) Tryptase Copy Number Variation (CNV) testing such as the one provided by Gene by Gene - ✔️

Tryptase copy number variation testing is the most targeted means of identifying multiple copies of TPSAB1. The US NIH partnered with Gene by Gene to design this testing and made it feasible for patients to become diagnosed.

2) Genotyping technology such as 23andMe, Ancestry DNA, FamilyTreeDNA, etc. - sometimes ✔️

However, this type of testing will often not be appropriately analyzed outside of research groups with specific skills and knowledge, and so will not report Tryptase CNV at the tryptase locus.

I'm hoping this will change soon.

3) Whole Exome Sequencing (WES) - ✔️

WES can identify multiple copies of TPSAB1. However, it will not be appropriately analyzed outside of research groups with specific skills and knowledge, and so will not report CNV at the tryptase locus (i.e., standard analysis of WES data will not correctly identify or report it).

4) Whole Genome Sequencing (WGS) - ❌

Standard analysis of WGS data will not correctly identify or report copies of TPSAB1.

IMPORTANT:

If you identify that any of the above information is no longer accurate, please let me know by sending a message to Contact Us. It is our sincere hope that at some time in the future, more of these testing modalities will identify Hereditary Alpha Tryptasemia by demonstrating multiple copies of TPSAB1.

ADDED 2025_02_23 

Hereditary Alpha Tryptasemia: Survey of Concomitant Genetic Testing, https://pubmed.ncbi.nlm.nih.gov/39965556/

"There was no clustering of genetic tests or relation to the inciting symptoms. Conclusion Genetic testing, often extensive, was obtained in 73% of these HαT patients. Most of these results were normal and did not suggest the presence of a concomitant genetic disorder."