Penalty and interest calculation on amended returns

As I recall from my long-ago IRS days, the Form 2210 penalty is always based on the tax shown on the original return, and is not recalculated when the return is amended (or audited).  There apparently have been some changes for corporations (Form 2220) regarding what is the tax shown on a prior year return, but the Internal Revenue Manual says that for individuals:

20.1.3.3.2 (03-31-2010)
Adjustments after Penalty Assessment
With the exception of SFR assessments, the estimated tax penalty is based on tax shown on the original return (or shown on a superseding return filed prior to the return due date). Therefore, most adjustments after penalty assessment are based on taxpayer requests for abatement.

And it then continues to describe how "abatement" requires more than "reasonable cause" as applied to other penalties.  

I assume you're more concerned about amended returns requesting a refund, rather than showing more tax owed (where additional ES penalty might be required).  Are you sure IRS will do that?  

Edited to add this excerpt from Notice 2021-8:

(3) Required annual payment based on original return. The required annual payment is based on the tax shown on the original income tax return (original return) for the taxable year, rather than the tax shown on any amended income tax return (amended return). In § 6654(d)(1)(B), the term “return for the taxable year” refers to the original return for the taxable year and does not refer to an amended return filed after the filing due date of the return for the taxable year. See, e.g., Mendes v. Commissioner, 121 T.C. 308, 324 (2003) (“We have repeatedly held that a taxpayer's estimated tax liability is based upon the taxpayer's tax liability as stated on the original tax return as filed. . . .”).