I am writing with a question about the variant listed in ClinVar with Variation ID 1935813. In ClinVar, this variant is associated with the following conditions: Marfan syndrome, familial thoracic aortic aneurysm, and aortic dissection.
I would like to clarify:
Does gnomAD have any data indicating that individuals carrying this variant were clinically diagnosed with Marfan syndrome or related FBN1-associated conditions?
How should the variant currently be interpreted in terms of pathogenicity or benignity, based on gnomAD population data?
Regarding the term “Condition” as used in ClinVar or similar databases, does it specifically refer to individuals who have both the variant and the disease, or is it primarily the context in which the variant was reported/evaluated?
Any clarification on these points would be greatly appreciated.
For your first question: unfortunately, we do not have comprehensive metadata on gnomAD samples, nor can we share phenotype information (see previous response here).
For questions two and three: the gnomAD team produces and maintains the gnomAD resource; we cannot comment on external tools. In addition, clinical variant classification is outside of our realm of expertise.
We wanted to mention another resource that might be of interest. GenomeConnect is an online registry developed by the Clinical Genome Resource (ClinGen) for people who are interested in sharing de-identified genetic and health information to improve understanding of genetics and health. For anyone who has had genetic testing, you can share your test results. The GenomeConnect team will share the variant(s) with approved users and databases included a large database of clinically interpreted variants, ClinVar. They also will let you know if the classification has changed by the lab that issued your report if you select to receive updates. GenomeConnect will also allow you to connect with other registrants based on diagnosis, gene, and US State. You can learn more about GenomeConnect here.