Variant identified, What next?

Question

[luffy]

I have been working on germline disorders and i have identified variants, classified and clinically correlated. My question is what are the other avenues that can be pursued after variants are detected? of course next logical step would be functional analysis, but one has to use computational analysis, what would it be?

Does downloading the public available data (RNA seq) and do the expression analysis and try to correlate the pattern with variants identified make sense since the RNA seq data are not available?

Thank you for your time
Any thoughts/opinion/suggestions would be appreciated

[Shred]

Which is the (biological) question you want to answer?

[luffy]

The question i am trying to answer/explore is some patients for whom variant of uncertain significance is detected and some patients with similar variant (same gene, close proximity to the VUS, clinical phenotype, zygosity etc) detected classified as pathogenic/likely pathogenic, for these cases can there be any pattern in the RNA level possibly.

[tomas4482]

Search "Expression quantitative trait loci". It sounds like you are looking for eQTL analysis.

Answer 1

[tomas4482]

Read more papers. You are asking questions related to study design/research logic rather than technical/biological issues. No one can help you because you are the only one who knows what should be done.

[luffy]

@tomas4482 thank you for your response, Yes i am reading and in the mean time i had posted.

Answer 2

[ahmad mousavi]

You can try wannovar website.

Or for prioritization of the variations you can use ACMG paper for finding the most relevant variations.

[luffy]

@ahmad mousavi, Thank you for your response, Yes i have already prioritised and classified the variants based on the updated ACMG/AMP recommendations and genotype-phenotype correction analysis.