Question regarding extension vs frameshift

[Nicole Kaetterhenry]

I have an interesting case where I have a single base duplication that occurs close to, but still just a bit 5' of the stop codon. It is my understanding that if the DNA is affected upstream of the stop codon that the resulting protein effect should be described as a frameshift and noted that it is a protein elongation and not a premature termination in our description of the variant on our report.  

My question, though, is that the first amino acid affected in this situation is the stop codon.  The amino acid where the duplication occurs remains the same, as does the next amino acid. The stop codon is the next in line in reference and is therefore the first aa to change.  I am thinking this would still be described as a frameshift, but I am not sure.  Alamut's predicted effect is calling an extension, but often Alamut I feel is not 100% correct in regard to HGVS nomenclature when looking at a variant that is close to or spans an exon/intron border or the end of the gene.  

The variant I am looking at is c.2006dup

Thank you for any advice you can provide. 

Nicole Kaetterhenry, BS MLS(ASCP)

Associate Clinical Curation Scientist - Post Analytical [PVT]]

PreventionGenetics | 3800 S Business Park Ave, Marshfield WI 54449

 
Part of the laboratories of Exact Sciences

  

Our vision is to improve lives through genetic testing.

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[Johan den Dunnen]

Dear Nicole,

unfortunately you do not give a variant description at DNA level, which helps me to answer your question. Based on the data you give, I assume the variant is NC_000017.11:g.82030798dup NM_144999.2:c.2006dup. Online tools Mutalyzer and Variant Validator both give as the predicted consequences on protein level p.(Ter671ValextTer10). Indeed, following HGVS nomenclature the variant at protein level is an extension (definition: a sequence change extending the reference amino acid sequence at the N- or C-terminal end with one or more amino acids). 

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)

Op donderdag 30 oktober 2025 om 15:19:43 UTC+1 schreef Nicole Kaetterhenry:

[Nicole Kaetterhenry]

Good afternoon.  I wanted to reach out again as I was holding the current case/report in hopes to receive guidance on how to properly notate the predicted effect for my patient.  If someone is able to assist, I would greatly appreciate it.  

Best,

Nicole Kaetterhenry, BS MLS(ASCP)

Associate Clinical Curation Scientist - Post Analytical [PVT]]

PreventionGenetics | 3800 S Business Park Ave, Marshfield WI 54449

 
Part of the laboratories of Exact Sciences

  

Our vision is to improve lives through genetic testing.

Learn more at PreventionGenetics.com

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From: Nicole Kaetterhenry <nkaett...@exactsciences.com>
Sent: Thursday, October 30, 2025 9:19 AM
To: hgvs-nom...@googlegroups.com <hgvs-nom...@googlegroups.com>
Subject: Question regarding extension vs frameshift

 

[Johan den Dunnen]

Dear Nicole,

not sure what you need, I have answered your question on Oct.31. A copy of my reply below.

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)

...unfortunately you do not give a variant description at DNA level, which helps me to answer your question. Based on the data you give, I assume the variant is NC_000017.11:g.82030798dup NM_144999.2:c.2006dup. Online tools Mutalyzer and Variant Validator both give as the predicted consequences on protein level p.(Ter671ValextTer10). Indeed, following HGVS nomenclature the variant at protein level is an extension (definition: a sequence change extending the reference amino acid sequence at the N- or C-terminal end with one or more amino acids). 

Op vrijdag 7 november 2025 om 23:43:50 UTC+1 schreef Nicole Kaetterhenry: