Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001071279 | SCV001236574 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2022-11-22 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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: 864161). This variant is also known as 555_556dupGGT and c.342_343dupGGT. This variant has been observed in individuals with clinical features of von Hippel-Lindau (VHL) syndrome (PMID: 17024664; Invitae). This variant is not present in population databases (gnomAD no frequency). This variant, c.341-1_342dup, results in the insertion of 1 amino acid(s) of the VHL protein (p.Gly114dup), but otherwise preserves the integrity of the reading frame. |
Ambry Genetics | RCV004030782 | SCV005036784 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-16 | criteria provided, single submitter | clinical testing | The c.341-1_342dupGGT variant results from a duplication of 3 nucleotides between positions 341-1 and 342 and involves the canonical splice acceptor site before coding exon 2 of the VHL gene. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing; however, the exact impact of this duplication on VHL splicing and function is currently unknown. The canonical splice acceptor site is well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |