Assistance with HGVS Nomenclature

[Chiraz Mehemmai]

Hi !

I would like some guidance on how to correctly write the HGVS nomenclature for the following variant:

NM_005228.5(EGFR):c.2155G>N p.(Gly719Xaa)

is it correct!

Specifically, I need help with:

- How to represent an unspecified nucleotide change at c.2155 in HGVS format

-How to correctly denote the predicted protein effect (p.(Gly719Xaa)) when the nucleotide substitution is not fully defined (c.2155G>A p.(Gly719Ser), ^c.2155G>T p.(Gly719Cys),^c.2155G>C p.(Gly719Arg).

Any advice or reference to official HGVS guidelines would be greatly appreciated.

Thank you, 

Chiraz Mehemmai

[Johan den Dunnen]

Dear Chiraz,

regarding your questions;

> - How to represent an unspecified nucleotide change at c.2155 in HGVS format

according to the HGVS nomenclature "Standards" page (see https://hgvs-nomenclature.org/stable/background/standards/, an unknown nucleotide on DNA level is described using "N".

The description "G>N" indicates that also no change (G>G) is an option, i.e. no change. When you are sure there is a change, the format to use is "G>H" (H = A, C, or T).

> How to correctly denote the predicted protein effect (p.(Gly719Xaa)) when the nucleotide substitution is not fully defined

Indeed HGVS nomenclature uses "Xaa" to indicate an unknown amino acid.

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)

Op zaterdag 29 november 2025 om 08:57:48 UTC+1 schreef mehe...@gmail.com: