Clarification on Reporting COL1A1 Variants

[Ligia Raquel Lameiras]

Dear HGVS group,

I would like to ask for your help regarding the most appropriate way to report the following variants detected in the COL1A1 gene.

In the BAM file, as seen in the image below, four consecutive alterations are visible:

1. DelAA
• c.3383_3384del p.(Glu1128Alafs*45)
2. InsCTCTG
• c.3385_3386insCTCTG p.(Gln1129Profs*112)
3. InsC
• c.3389_3390insC p.(Pro1131Serfs*43)
4. InsTGT
• c.3391_3392insTGT p.(Pro1131delinsLeuSer)
  
  

Should these be reported as NM_000088.4:c.3383_3391delinsCCTCTGAAGGCTCTGT p.(Glu1128Alafs*48), or is there a more appropriate way to describe them?

Thank you in advance for your assistance.

Best regards,

Lígia Lameiras

Lígia Raquel Correia Lameiras

Operations - Pathology & Genetics

Sequencing Dry Lab 

 

P Think before you print

 

AVISO DE CONFIDENCIALIDADE: Este e-mail e quaisquer ficheiros informáticos com ele transmitidos são confidenciais e destinados ao conhecimento e uso exclusivo do respectivo destinatário, não podendo o conteúdo dos mesmos ser alterado. Caso tenha recebido este e-mail indevidamente, queira informar de imediato o remetente e proceder à destruição da mensagem. 

DISCLAIMER: This e-mail and any files transmitted with it are confidential and intended solely for the use of the individual or entity to whom they are addressed. Their contents may not be altered. If you are not the intended receiver, please notify the sender and destroy it immediately. 

[Johan den Dunnen]

Dear Ligia,

a difficult case which shows the limitations of HGVS nomenclature, i.e. for complex variants it becomes nearly impossible to give recommendations that will cover all possibilities.

Following current recommendations, incl. the fact that proposal SVD_WG010 will be rejected, the variant should be described as NM_000088.4:c.[3383_3384del;ins3385_3386insCTCTG;3389_3390insC;3391_3392insTGT] r.(?) p.[(Glu1128_Gln1129delinsAlaSerGlu);(Pro1131SerfsTer44)]. This follows the rule that variants which in flanking residues should be described as delins.

Given the fact that on protein level twice two variants are merged, you might prefer to describe the variants on DNA level as NM_000088.4:c.[3383_3385delinsCCTCTG;3390_3391delinsCTCTGT] r.(?) p.[(Glu1128_Gln1129delinsAlaSerGlu);(Pro1131SerfsTer44)]

The description NM_000088.4:c.3383_3391delinsCCTCTGAAGGCTCTGT p.(Glu11.28Alafs*48) does not follow current recommendations.

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)

Op zaterdag 1 maart 2025 om 12:06:52 UTC+1 schreef Ligia Raquel Lameiras: