Two variants in cis

[Rachel Challis]

Dear team,

We identified two variants in LDLR(NM_000527.5) gene in NGS data: c.2013_2014insA and c.2020_2025del. The read data shows that they are in cis. I wanted to confirm the correct way to report them. As they're separated by more than 1 bp should they be reported as:

c.[2013_2014insA;2020_2025del]?

Or should we consider as 1 and use c.2014_2023delinsACTGA?

Then for the protein consequence would this then be:

p.[(Leu672ThrfsTer45;Asn674_Gly675del)] or can we shorten to p.(Leu672ThrfsTer43)?

Thank you for your help.

BW Rachel

[Johan den Dunnen]

Dear Rachel,

indeed, following HGVS nomenclature the variant can be described as NM_000527.5:c.[2013_2014insA;2020_2025del]. However, to ensure a correct description of the predicted consequences on protein level, NM_000527.5:c2014_2023delinsACTGA p.(Leu672ThrfsTer43) seems more appropriate.

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)

Op maandag 18 augustus 2025 om 14:30:04 UTC+2 schreef Rachel Challis: