Assessed by IARC on November 18, 2019 during meeting 45.

The committee considered IGHV2-70*01_S6619 (A124G) of Genotype B12 of submission S00010, which was previously evaluated as IGHV2-70*01_S4660 of submission S00004 at Meeting 8. It was affirmed as a Level 0 sequence at that time.

The sequence was seen in just 0.05% of all unmutated rearrangements, with 296 sequences including 93 perfect matches to the inferred allele. There was abundant variation in the CDR3 regions of the aligned sequences. Two other alleles were present in the genotype, and it is possible that one of these three sequences is an IGHV2-70D sequence. Haplotype data is supportive of the inference, but in light of the very low frequency of rearrangements seen and the complicated haplotype of this subject, it was affirmed as a Level 0 sequence. The sequence was affirmed up to and including nucleotide 319 even though alleles of IGHV2-70/IGHV2-70D in general extend up to and including base 322. However, the nucleotide composition of the subsequent three bases of genes associated with this inferred allele did not support their inference. It is however likely that three additional 3’ nucleotides are present in the sequence, and this is indicated in IARC and OGRDB publications by three dots at the end of the sequence.

At the IARC Meeting 68, April 26th 2021, it was agreed that sequences affirmed by the IARC as Level 0 sequences, that subsequently have entered the IMGT germline gene database by other means, should be elevated to Level 1.

At the IARC Meeting 69, May 18th 2021, IGHV2-70*i01 was elevated to Level 1. This sequence was incorporated into the IMGT germline gene database as a consequence of the IMGT-NC Report #2020-2-1008 (October 8th, 2020). The sequence was submitted to IMGT by Abdullah Gamal Dorgham, William Sinclair Gibson, Oscar Rodriguez and Corey Watson. The sequence recorded in OGRDB remains the sequence that was affirmed as the original IGHV2-70*i01 sequence. The sequence that is now recognized as IGHV2-70*20 includes the final three nucleotides of the sequence – TAC.