Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000551115 | SCV000626870 | pathogenic | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2017-12-15 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 2-3 of the VHL gene. The 5' boundary is likely confined to intron 1. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. Deletions of exons 2-3 have been reported several in individuals with von Hippel-Lindau (VHL) syndrome (PMID: 19336503, 17661816, 12114495, 19764026). This deletion includes the elongin binding domain of VHL, which is required for protein stability and tumor suppressive activity (PMID: 14987375, 10900011). There are also several pathogenic missense and loss-of-function variants encompassed by this deletion in individuals with VHL, further demonstrating the importance of this region (PMID: 8707293). For these reasons, this variant has been classified as Pathogenic. |