When you upload a new sketch to a SAMD board, the serial port list drops your port choice and chooses the one above it when the board is reset for upload.

Steps:

1. Open new sketch
2. Choose board and port
3. Upload to a SAMD board
4. Note the serial port choice after upload. It will be the one above your port in the list.

This causes confusion when you try to open the serial port. You can open the port, but you have to re-choose it first.
MacOS Big Sur 11.2.3 20D91

This is related to an earlier issue, #271

NOTE: this only happens if the port above your board is a virtual port.
For example, if it is a BluetoothSerial port, it happens, but if you delete the reference to the BluetoothSerial device, and therefore the port, it doesn't happen. I tested using a BluetoothSerial HC-05 board.