text: user15221: EDIT
  By thinking over the issue, I realized it was mixing two linked but separate questions:
  
  Q1. How to handle the situation when there are divergences between a GenBank file and an actual or theoretical molecule:
  
  Should the difference be indicated in the feature table? If so, with which feature key? And if not, how should it be indicated or what should be done?
  
  Further, when indicating a divergence using a feature key, which should be considered the reference: the file or the molecule?
  
  
  
  Q2. How to keep track of changes between versions of a GenBank file when corrections or updates are made?
  
  
  I have thus re-titled the question accordingly, and by making further researches into the issues I found what seems to me the appropriate solutions (see my answer below).
  ORIGINAL QUESTION
  Background I am maintaining a database of sequence files describing a collection of bacterial strains and plasmids that we have in our lab.
  I am confronted to two sorts of issues:
  
  some sequence files contain errors (see comments below for examples of errors)
  other sequence files describe theoretical sequences of molecules that themselves contain variations (mutations, insertion or deletions) that occurred during the molecular cloning process.
  
  Objective I want to annotate the sequences to mark those errors and variations using the GenBank format. However, from the feature keys of the GenBank format described on the INSDC website, it is not clear to me which feature key should be used in each case, essentially this is either 'variation' or 'misc_description'.
  Example To better explain the confusion, here below are what seems to me the most relevant feature keys, and my comment of the problem I have with them:
  Feature key           variation
  Definition            a related strain contains stable mutations from the same
                        gene (e.g., RFLPs, polymorphisms, etc.) which differ
                        from the presented sequence at this location (and
                        possibly others);
  ...
  Comment               used to describe alleles, RFLP's,and other naturally 
                        occurring mutations and  polymorphisms;
                    >>> variability arising as a result of genetic 
                        manipulation (e.g. site directed mutagenesis) should 
                        be described with the misc_difference feature;
  
  According to the line marked >>> above, the feature key misc_difference should be used...
  Feature Key           misc_difference
  Definition            feature sequence is different from that presented in the
                        entry and cannot be described by any other difference
                        key (old_sequence, variation, or modified_base);
  ...
  Comment               the misc_difference feature key should be used to
                        describe variability that arises as a result of 
                        genetic manipulation (e.g. site directed mutagenesis);
                    >>> use /replace="" to annotate deletion, e.g.
                        misc_difference 412..433
                                        /replace=""  
  
  But now, according to the example marked >>> above, it means the variation (here a deletion) is NOT in the considered entry...
  Question So how are variations (mutation, insertion, deletion, errors) correctly described in Genbank given that are actually present in an entry ?
  
  user3848: Your core question is:
  
  (mutations, insertion or deletions) that occurred during the molecular cloning process.
  
  I asked NCBI directly and their response is:
  
  For natural genetic variation use 'Variation' feature;
  
  
  For 'artificial' genetic variation (lab-produced by genetic modification) then use 'misc_difference'.
  
  In summary in all scenarios its singly the 'misc_differences' that are used (see Conclusion).
  So in my scenario where I want to screen out targeted mutagenesis its the 'misc_difference', i.e. the second option of the two you present. This is also true in your second scenario because it is changes possibly unintentional, possibly random mutagenesis / or just unintentional errors during cloning. Finally, this is also true for SOME of the 'errors' you are reporting in comments:
  
  for the first i, ii and iii that appears to be just correcting stuff - administration, just cross-check with those submitting.
  for 'variations' the second i and ii in comments, that falls into the 'misc_difference', because a form of mutagenesis, albeit probably unintentional.
  
  
  Conclusion
  The 'variation' feature description isn't clear given the description you reported against NCBI's official Helpdesk response. Its a fair question, its a clear answer, but doesn't explain why the description is confusing.
  
  On 'errors' of mis-identification, e.g. correctly identified e.g. via local Blast or Blat, e.g. sequenced the wrong target, I would use an internal marker, e.g. returned to contributor for comment. Pass it back to the contributor and ask for their input and depending what they say simply mark the record in the 'Comments section' e.g. originally defined as XX. The contributor could have made all sorts of different errors, e.g. annotation - copied and pasted the wrong stuff - experimental anything and you need to give them a chance to respond. Uploading these records on an external database, i.e. Genbank, needs a joint agreement with all parties concerned because it is certainly valid information for someone.
  
  Note, the official blurb here, doesn't appear informative:
  
  Disrupted genes and gene fragments
  Sometimes a genome will have adjacent or nearby genes that seem to be
  only part of a protein. In many cases these indicate a possible
  problem with the sequence and/or annotation. A related issue is the
  presence of internal stop codons in the conceptual translation of a
  CDS that looks like it should be a real CDS. These problems may be due
  to a variety of reasons, including mutations or sequencing or assembly
  artifacts. They can be annotated in a number of ways:
  Annotate the gene with /pseudo to indicate that there is a problem
  with the gene. Note that this qualifier does NOT mean that the gene is
  a pseudogene. (see point 2, below, if it is known that the gene IS a
  pseudogene) If multiple gene fragments were present initially, then
  add a single gene feature which covers all of the potential coding
  regions and add the pseudo qualifier. If known, a note qualifier may
  be added indicating why this gene is disrupted, for example:
  
   1        200     gene
                           gene    phoA
                           gene_desc     alkaline phosphatase
                           locus_tag     OBB_0001
                           pseudo
                           note    nonfunctional due to frameshift
  
  
original_text: 15221: <h3>EDIT</h3>
  <p>By thinking over the issue, I realized it was mixing two linked but separate questions:</p>
  <ul>
  <li><p><strong>Q1. How to handle the situation when there are divergences between a GenBank file and an actual or theoretical molecule:</strong></p>
  <ul>
  <li><p>Should the difference be indicated in the feature table? If so, with which feature key? And if not, how should it be indicated or what should be done?</p>
  </li>
  <li><p>Further, when indicating a divergence using a feature key, which should be considered the reference: the file or the molecule?</p>
  </li>
  </ul>
  </li>
  <li><p><strong>Q2. How to keep track of changes between versions of a GenBank file when corrections or updates are made?</strong></p>
  </li>
  </ul>
  <p>I have thus re-titled the question accordingly, and by making further researches into the issues I found what seems to me the appropriate solutions (see <a href="https://bioinformatics.stackexchange.com/a/18978/15221">my answer</a> below).</p>
  <h3>ORIGINAL QUESTION</h3>
  <p><strong>Background</strong> I am maintaining a database of sequence files describing a collection of bacterial strains and plasmids that we have in our lab.</p>
  <p>I am confronted to two sorts of issues:</p>
  <ul>
  <li>some sequence files contain errors (see comments below for examples of errors)</li>
  <li>other sequence files describe theoretical sequences of molecules that themselves contain variations (mutations, insertion or deletions) that occurred during the molecular cloning process.</li>
  </ul>
  <p><strong>Objective</strong> I want to annotate the sequences to mark those errors and variations using the GenBank format. However, from the feature keys of the GenBank format described on the <a href="https://www.insdc.org/documents/feature_table.html" rel="nofollow noreferrer">INSDC website</a>, it is not clear to me which feature key should be used in each case, essentially this is either 'variation' or 'misc_description'.</p>
  <p><strong>Example</strong> To better explain the confusion, here below are what seems to me the most relevant feature keys, and my comment of the problem I have with them:</p>
  <pre><code>Feature key           variation
  Definition            a related strain contains stable mutations from the same
                        gene (e.g., RFLPs, polymorphisms, etc.) which differ
                        from the presented sequence at this location (and
                        possibly others);
  ...
  Comment               used to describe alleles, RFLP's,and other naturally 
                        occurring mutations and  polymorphisms;
                    &gt;&gt;&gt; variability arising as a result of genetic 
                        manipulation (e.g. site directed mutagenesis) should 
                        be described with the misc_difference feature;
  </code></pre>
  <p>According to the line marked <code>&gt;&gt;&gt;</code> above, the feature key <code>misc_difference</code> should be used...</p>
  <pre><code>Feature Key           misc_difference
  Definition            feature sequence is different from that presented in the
                        entry and cannot be described by any other difference
                        key (old_sequence, variation, or modified_base);
  ...
  Comment               the misc_difference feature key should be used to
                        describe variability that arises as a result of 
                        genetic manipulation (e.g. site directed mutagenesis);
                    &gt;&gt;&gt; use /replace=&quot;&quot; to annotate deletion, e.g.
                        misc_difference 412..433
                                        /replace=&quot;&quot;  
  </code></pre>
  <p>But now, according to the example marked <code>&gt;&gt;&gt;</code> above, it means the variation (here a deletion) is NOT in the considered entry...</p>
  <p><strong>Question</strong> So how are variations (mutation, insertion, deletion, errors) correctly described in Genbank given that are actually present in an entry ?</p>
   3848: <p>Your core question is:</p>
  <blockquote>
  <p>(mutations, insertion or deletions) that occurred during the molecular cloning process.</p>
  </blockquote>
  <p>I asked NCBI directly and their response is:</p>
  <blockquote>
  <p>For natural genetic variation use 'Variation' feature;</p>
  </blockquote>
  <blockquote>
  <p>For 'artificial' genetic variation (lab-produced by genetic modification) then use 'misc_difference'.</p>
  </blockquote>
  <p>In summary in all scenarios its singly the 'misc_differences' that are used (see Conclusion).</p>
  <p>So in my scenario where I want to screen out targeted mutagenesis its the 'misc_difference', i.e. the second option of the two you present. This is also true in your second scenario because it is changes possibly unintentional, possibly random mutagenesis / or just unintentional errors during cloning. Finally, this is also true for SOME of the 'errors' you are reporting in comments:</p>
  <ul>
  <li>for the first i, ii and iii that appears to be just correcting stuff - administration, just cross-check with those submitting.</li>
  <li>for 'variations' the second i and ii in comments, that falls into the 'misc_difference', because a form of mutagenesis, albeit probably unintentional.</li>
  </ul>
  <hr />
  <p><strong>Conclusion</strong>
  The 'variation' feature description isn't clear given the description you reported against NCBI's official Helpdesk response. Its a fair question, its a clear answer, but doesn't explain why the description is confusing.</p>
  <hr />
  <p>On 'errors' of mis-identification, e.g. correctly identified e.g. via local Blast or Blat, e.g. sequenced the wrong target, I would use an internal marker, e.g. <code>returned to contributor for comment</code>. Pass it back to the contributor and ask for their input and depending what they say simply mark the record in the 'Comments section' e.g. <code>originally defined as XX</code>. The contributor could have made all sorts of different errors, e.g. annotation - copied and pasted the wrong stuff - experimental anything and you need to give them a chance to respond. Uploading these records on an external database, i.e. Genbank, needs a joint agreement with all parties concerned because it is certainly valid information for someone.</p>
  <hr />
  <p>Note, the official blurb <a href="https://www.ncbi.nlm.nih.gov/genbank/genomesubmit_annotation/#disrupted_genes" rel="nofollow noreferrer">here</a>, doesn't appear informative:</p>
  <blockquote>
  <p>Disrupted genes and gene fragments</p>
  <p>Sometimes a genome will have adjacent or nearby genes that seem to be
  only part of a protein. In many cases these indicate a possible
  problem with the sequence and/or annotation. A related issue is the
  presence of internal stop codons in the conceptual translation of a
  CDS that looks like it should be a real CDS. These problems may be due
  to a variety of reasons, including <strong>mutations</strong> or sequencing or assembly
  artifacts. They can be annotated in a number of ways:</p>
  <p>Annotate the gene with /pseudo to indicate that there is a problem
  with the gene. Note that this qualifier does NOT mean that the gene is
  a pseudogene. (see point 2, below, if it is known that the gene IS a
  pseudogene) If multiple gene fragments were present initially, then
  add a single gene feature which covers all of the potential coding
  regions and add the pseudo qualifier. If known, a note qualifier may
  be added indicating why this gene is disrupted, for example:</p>
  </blockquote>
  <pre><code> 1        200     gene
                           gene    phoA
                           gene_desc     alkaline phosphatase
                           locus_tag     OBB_0001
                           pseudo
                           note    nonfunctional due to frameshift
  </code></pre>
  