Nomenclature dup frameshift and extension

[Irina RB]

Dear Johan,

When a variant alters the reading frame and, as a result, removes the canonical stop codon—leading to an extension of the protein with a new stop codon located in the 3′UTR—should we described as a frameshift variant, am I right?

For reference, the variant in question is:
(GRCh38) NM_000503.6: c.1656_1659dup (p.Ile554CysfsTer79)

Best regards,
Irina

[Johan den Dunnen]

Dear Irina,

you are right, the predicted consequence of the variant you give (NC_000008.11:g.71211196_71211199dup NM_000503.6:c.1656_1659dup) at the protein level is p.(Ile554CysfsTer79).

Please note the HGVS nomenclature definition of "extension" is "a sequence change extending the reference amino acid sequence at the N- or C-terminal end with one or more amino acid" (see https://hgvs-nomenclature.org/stable/background/glossary/). 

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)

Op dinsdag 14 oktober 2025 om 11:41:47 UTC+2 schreef Irina RB: