My tax penalty was $49. After annualizing my data my penalty went up to $225! How/why did that happen?

If you haven't already. go back through the Underpayment Penalty questionnaire and check your responses.

To review underpayment penalties, in TurboTax Online:

1. Open return and choose Other Tax Situations
2. Choose Underpayment Penalties
3. If asked "do you want to review estimated taxes" choose Yes

You could also try deleting Form 2210, Underpayment of Estimated Tax, and then revisiting that section.

Here's the procedure for deleting unwanted forms, schedules, and worksheets in TurboTax Online:

1. Open or continue your return in TurboTax.
2. In the left menu, select "Tax Tools" and then "Tools".
3. In the pop-up window Tool Center, select "Delete a form".
4. Select "Delete" next to the form you wish to delete.

See this TurboTax tips article for more information about Form 2210 and this one regarding the penalty.