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Not Updated For Current Season
The masteries shown here are not yet updated for the current season, the guide author needs to set up the new masteries. As such, they will be different than the masteries you see in-game.
While playing twitch for a while as a glass cannon, which is the way most people seem to play him, I've started building him more tank to survive teamfights, and being able to take on tanky dps on early game.
Due to the fact that twitch gains a large amount of ranged haste from abilities and "expunge" which have a high base damage allows him to build for survivability early game while still having good damage.
I've played this only in normal games, but it seems to be a better and a more fun way to play twitch.
Red runes are kinda self-explainatory.
Yellow runes is either armor or health just for the survivability. I take health since it improves atma's and you get alot of armor with this build. Mana-regen is not needed in my opinion.
Blue runes is magic resist just for more survivabilty, while there isnt any other that is really good with him.
Quintessence runes is armor penetration just for the added damage early game, but could also be replaced by run speed.
I go either defense or attack masteries. Both masteries seems equally good to me. It is just a question of preference.
I usually take Doran's Blade for a starter item. But I you find yourself in a hard lane, taking regen items or a Doran's Shield might be better. But the damage you get from it is quite nice while you are farming and building defensive items.
I usually go back at around 1000g and buy myself a pair of Beserker's Greaves and pots/wards if I feel its needed. You get yourself some much needed mobilty and attack speed.
While some might prefer Boots of Mobility for the roaming through lanes, I find that you would need some extra damage while get your survivability.
Next items is 1x Heart of Gold, which I used to stack before the nerf, and a Catalyst the Protector. Which will give some much needed survivability now early in the game, and grant you lane staying power and some gold regen.
Next item will be a offensive one. Either Wit's End, which is especially good against a team with low mana and AP reliant, or Youmuu's Ghostblade.
After that you would start finishing you defensive items, building Heart of Gold into Randuin's Omen and Catalyst the Protector into Banshee's Veil. The order which you build the is decided by whether they have strong physical or magic damage.
The two last items while be Atma's Impaler and Last Whisper.
You while now have around 2,9k hp, 200 armor, 150 mr and 200 ad + 49 magic damage from wit's end + 65% attack speed.
I find Flash and Ignite to be the two best summoner spells for this.
Ignite makes you way more dangerous in early laning, and helps kill the lifesteal from carries with it or casters who can drain.
Flash is a pretty good oh **** button, which helps you restealth while geting chased,