Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV001092964 | SCV001249721 | likely pathogenic | not provided | 2019-09-01 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002554860 | SCV002997379 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2022-05-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu37*) in the VHL gene. It is unclear whether it will result in an absent or disrupted protein product because an in-frame methionine located at codon 54 has the potential to rescue this variant. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with VHL-related conditions. ClinVar contains an entry for this variant (Variation ID: 872483). Several studies have shown that the VHL protein created from a downstream methionine located at codon 54 is biologically active, and exhibits properties similar to the full-length, wild-type protein (PMID: 9671762, 9751722). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |