HGVS listing of multiple RNA and protein consequences

[Kunc Lorena]

Dear HGVS group,

 

Based on mRNA analysis, we have shown that a single DNA variant results in three different aberrant transcripts, leading to three protein products: a nonsense change, a frameshift, and a missense change.

 

Could you please advise on the correct way to list these consequences?

 

Should the RNA changes be described using a single r.[…], for example r.[171_185del,171_195del,172g>u], or should each RNA change be listed separately as [r.171_185del, r.171_195del, r.172g>u]?

 

Should the protein changes be described individually as p.(Trp57*), p.(Trp57Cysfs14), p.(Asp58Tyr), or listed together as p.[Trp57,Trp57Cysfs*14,Asp58Tyr]?

 

Thank you in advance.

 

Kind regards,

Lorena Kunc

 

Lorena Kunc, M.Sc.

Department of Molecular Diagnostics

Institute of Oncology Ljubljana

 

[Johan den Dunnen]

Dear Lorena,

following HGVS nomenclature all variants should be described at genomic level, descriptions at other level may be added. Since you do not give a reference sequence, I can not answer your question (nor check my answer).

My best guess is the variant should be described as NC_0000aa.b:g.#G>T (or NC_0000aa.b:g.#C>A) NM_ccccccc.d:c.#G>T r.[171_185del,171_195del,172G>T] p.[Trp57Ter,Trp57CysfsTer14,Asp58Tyr] where # is a nucleotide position. Note I use "G>T" and not "g.u" because there will be an upcoming nomenclature change covering this format.

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)

Op woensdag 14 januari 2026 om 13:29:59 UTC+1 schreef Kunc Lorena: