description of a triplication

[Claudia Pinato]

Dear HGVS support,

I have a question about the description in case of  triplication.

I found with NGS and MLPA analysis 4 total copies of exon 4 to exon 6 of MLH1 gene.

I was not able to detemine if it is in tandem or not, so I think I should use the format like g.?_?ins[NC....] but how should I indicate in the formula that it is not just an insertion of one copy but of two?

Thanks for your help

Claudia

--

Dr. Claudia Pinato, PhD
Biologist, Specialist in Medical Genetics
Hereditary Tumor Unit - Veneto Institute of Oncology IRCCS

[Johan den Dunnen]

Dear Claudia,

yes, following current recommendations, you should also indicate you detected 4 copies. While for the detection of 3 copies the format g.?_?ins[NC_000003.12:g....] can be used, for 4 copies things get more complex since these two additional copies can be anywhere in the genome, even on different chromosomes or even one on each of the two alleles. The only suitable format I can think of for this situation is that described on the Alleles page (https://hgvs-nomenclature.org/stable/recommendations/DNA/alleles/) under "uncertain phase" so like g.?_?ins[NC_000003.12:g....](;)g.?_?ins[NC_000003.12:g....].

Best regards,

Johan den Dunnen
HUGO HGVS Variant Nomenclature Committee (HVNC)

Op zaterdag 1 maart 2025 om 12:07:25 UTC+1 schreef claudia...@iov.veneto.it: