N_xClinical offers up-to-date annotations and link outs to several online databases, including RefSeq, ClinGen, and OMIM®, to aid interpretation. An overwhelming majority of the time, the annotations in N_xClinical and these online databases will give identical gene name and genomic coordinates with complimentary information for final review. However, occasionally some gene searches do not always yield the expected results, as happened with a recent sample case review involving the gene IGH.

A sample for review with N_xClinical included a detailed search on several immunoglobulin (IG) genes, including IGH. Searching for IGH in the N_xClinical search panel yielded no results. Further investigation revealed that IGH is NOT an approved official RefSeq gene, but rather a proposed gene. By design, the N_xClinical gene track contains only RefSeq approved genes. However, as the OMIM gene track displays all OMIM approved genes, which includes many RefSeq proposed genes, IGH was listed in this track at 16p11.2

Upon clicking on the OMIM link for more information, the OMIM IGH record indicates the cytogenetic location to be 14q32.33 and RefSeq lists the same. What is going on here?!

If we take a further look at the details of OMIM, we find the genomic coordinates listed (14:105,586,436-106,879,843) were taken directly from NCBI/RefSeq but are for GRCh38. Both of these web versions have switched to the newest genome build, while most commercial arrays are still mapped to build GRch37/hg19. A quick search of IGH on the UCSC genome browser confirms that IGH was in fact remapped from 16p11.2 to 14q32.33 between these two genome builds.

So remember, always check your genome build when you find potential genomic coordinate discrepancies and don’t hesitate to contact Support if you have any questions about N_xClinical!