Hi,
Thank you for posting in Symantec community.
I would be glad to answer your query.
Would it be safe to exclude the MS Office directory
--> Though it's not suggested you can exclude but check if you really see any performance improvement. I don't think there would be noticeable change. When we talk about security even though you exclude MS office from scan it doesn't mean SEP will not detect threat if there is any.
If there is any threat inside MS office application SEP will definitely detect.
Do you see any performance issue with scheduled scan or manual scan?
There is one setting which we do recommend to the customer when he face slowness issue with MS office application. Uncheck the option scan when a file is modified.