Linking Genetic Variants to Measurable Changes In The Body

How to turn raw data into clinical insight

In previous posts, we have captured variants in VCF (Variant Call Format) files and annotated them with known effects. But how do we turn thousands of raw mutations into clear clinical insight?

Here's a sample line from an annotated VCF.

chr13 32316432 . A G . PASS CSQ=...|ASS1|...|Pathogenic|Citrullinemia_type_I

Once annotated, a single VCF line turns from raw data into a call to adventure. It tells us

• which gene is affected (`ASS1`),

• what type of mutation it is (`A ➜ G`: the base change),

• whether it is known to be “pathogenic”, i.e. clinically classified as harmful, and

• which disease it is associated with (`Citrullinemia type_I`)

So, this entry flags a mutation in the ASS1 gene linked to the citrullinemia type 1 disease. But it doesn't yet tell us the whole story. How does this disease relate to the patient's symptoms?