With Thetis I used VAC1 to connect to a USB mic and USB speakers. I used VAC2 with RX2 for digital modes (DIGU) going to Virtual audio cable pair with WSJTX at the other end. The other SDR apps have dedicated mic and audio assignment slots for mic and speaker. At least this is what I figured out/read about Thetis config so far, working good here.
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More specifically, to get my speakers and mic working on VAC1 I found I had to use MME with MSFT Sound Mapper for best results, this is for my Windows 10 Pro x64 on a HP laptop.
For VAC2 I am using VAC cables.

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