In using normalizer, we ran into an issue with p. prediction/generation for two delins that involved more than one codon. In both cases, Normalizer normalized the c. as two dels separated by a single retained nt and the p. was generated as p.?, even though the correct predicted affected protein sequence is shown.
Questions:
(1) is the normalization to two dels separated by a single retained nt intentional? I realize that it is arguably the correct HGVS nomenclature for delins that span multiple codons, although the SVD-WG has prepared a proposal to modify (SVD-EG010).
(2) if the normalization is intentional, is there a plan or timeline to adopt the SVD-WG proposal?
(3) is it intentional that p.? is generated even though the correct predicted affected protein sequence is shown?
(4) Is there another way to get a p. prediction for these types of variants?
The proposal has not been accepted yet, partly because of some fundamental concerns raised by our team. We are currently working on a revision of this proposal together with the SVD-WG / HVNC committee.
This is mainly because there are no rules to generate complex protein descriptions, such as the ones typically resulting from allele descriptions (compound variants). We do have a number of ideas, but we do not have any implementations yet.
There are multiple ways to get a description, e.g., by using Mutalyzer 2, which does not attempt to decompose and/or recombine an input description. This may give a satisfactory (maybe even correct) answer in this case, but in general, it will not.
In using normalizer, we ran into an issue with p. prediction/generation for two delins that involved more than one codon. In both cases, Normalizer normalized the c. as two dels separated by a single retained nt and the p. was generated as p.?, even though the correct predicted affected protein sequence is shown.
Examples: https://mutalyzer.nl/normalizer/NM_000038.5:c.1997_1999delTACinsA https://mutalyzer.nl/normalizer/NM_000038.5:c.497_499delCTAinsTT
Questions: (1) is the normalization to two dels separated by a single retained nt intentional? I realize that it is arguably the correct HGVS nomenclature for delins that span multiple codons, although the SVD-WG has prepared a proposal to modify (SVD-EG010). (2) if the normalization is intentional, is there a plan or timeline to adopt the SVD-WG proposal? (3) is it intentional that p.? is generated even though the correct predicted affected protein sequence is shown? (4) Is there another way to get a p. prediction for these types of variants?
Many thanks, Heather