Not exactly once, but generally only once.

There is a line of actions the game takes.

Step 1. Base damage on the skill, and all damage amplifiers within the skill line itself. Example for Panetti’s, would be Panettis base damage, and Supercharge amp of 80%. You then have Panneti’s base damage (lets say 20, just for easy math), + 80% elemental boost, resulting in 36.

Step 2. Transmuters directly attached to the skill. Think Tainted Ray.

Step 3. Gear and buff applied conversions. IEE, Reckless Power, Warpfire, Blood Orb, Clarivoyant Set, ect, are all applied at the same exact time in the damage conversions. Don’t know the exact order of two things try to modify the same value, but I think it prioritizes gear innate conversions over buffs IIRC, meaning if you are using Warpfire, and Blood Orb, Your cold damage will convert to fire, and everything else will convert to chaos. It’s a bit messy to figure out overall.

- All non inner-skill based damage multipliers are applied, from all sources. Effectively, your total +% to X damage types.

Going back to Panetti’s demo idea, assuming you have +900% Chaos damage, and convert Panetti’s to Chaos via Blood Orb, you multiply that into base Panetti damage (20) by the +900%, so 200, plus the bonus +80% you got from Supercharged, or 16, for a total of 216 damage, all applied as Chaos damage. Now obviously Panettis doesn’t have 20 base damage except at very low ranks, but we just wanted easy math and 20 gave us easy math.

We can also use Panetti’s for a far more complicated conversion discussion, the idea of how Warpfire interacts within the Panetti line.

Step 1, Base Panetti’s, lets assume 60 damage for clean numbers, and a perfect 100% conversion from Warpfire (Don’t know if Warpfire has potential for a 100% roll or not, but clean math trumps all for this explanation so lets assume it does). We pick up Distortion, which for clean math, lets say grants a flat +100% fire damage to Panetti’s. This increases base Panetti damage to 20 cold, 20 Lightning, 40 Fire.

- Warpfire is applied, converting Cold into Fire. Here, we see Panettis has +100% fire damage, so where do we apply it? We apply it before we convert, meaning we end up with 60 (20 from Distortion, 40 Base) Fire, 20 Lightning, not 80 Fire, 20 Lightning, as if Warpfire applied first.

Really complicated territory here, with multiple parts of the Panetti’s tree skill line, with clean math numbers.

Base Panetti 60 damage, 20 Fire, 20 Cold, 20 Lightning. Distortion, Supercharged, both applying a +100% bonus (Meaning 200% fire 100% cold 100% Lightning), and Warpfire applying a 100% cold to fire conversion. Step 1, Apply all damage amplifiers. Fire 60(20 Base + 40 Bonus), Cold 40 (20 base + 20 Bonus), and Lightning 40 (20 base + 20 Bonus). Warpfire applied, and we change to Fire 100 (20 base, 40 bonus, C to F 20 base, C to F 20 Bonus), Lightning 40 (20 Base, 20 Bonus).

Assuming we decide to NOW apply the +900% fire damage you just happen to have sitting around as your multplier, here is the results we get.

Fire 460 (20 base Fire+900%, 40 bonus fire damage, CtF 20+900%, CtF 20 Bonus).