switching from cDNA to RNA numbering

marco.m...@iov.veneto.it

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Jan 13, 2025, 9:31:25 AMJan 13

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Dear Mutalyzer team,

it happens that the cDNA and RNA numbering for a given exon do not match.

For example, the deletion of exon 5 of CHEK2 is indicated as c.593_683del (NM_007194.3) at the cDNA level.

Querying the mutalizer with this deletion returns the RNA description as r.594_684del (NM_007194.3).

I can't figure out the reason for this one-nucleotide change.

This switch is apparently exon-specific, as it doesn't happen for other exons of the same gene. Has it something to do with the coding frame?

Thank you very much

Marco

Mihai Lefter

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Jan 13, 2025, 10:05:04 AMJan 13

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Dear Marco,

Thank you for using Mutalyzer and for reaching out to us regarding this issue.

The input description `NM_007194.3:c.593_683del` has been normalized according to the 3' rule to `NM_007194.3:c.594_684del`. From this, the RNA prediction `NM_007194.3:r.(594_684del)` is derived [1].

Best regards,
Mihai

[1]: https://mutalyzer.nl/normalizer/NM_007194.3:c.593_683del

marco.m...@iov.veneto.it

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Jan 13, 2025, 11:56:02 AMJan 13

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Hi Mihai,

thank you for the fast reply.

I just realized that the exceprion to the 3' rule when dealing with deletions in exon/exon boundaries does not apply for RNA description according to HGVS!