Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001373116 | SCV001569820 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2022-10-27 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 1 of the VHL gene. It is not expected to change the encoded amino acid sequence of the VHL protein. However, this sequence change falls within a cryptic exon in the VHL gene, known as exon E1’, which is naturally expressed at low levels in several human tissues (PMID: 29891534). RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals affected with VHL-related conditions. 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. Studies have shown that this variant is associated with altered splicing resulting in unknown protein product impact (Invitae). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1063292). |