Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002420064 | SCV002726209 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-06-22 | criteria provided, single submitter | clinical testing | The c.204dupG pathogenic mutation, located in coding exon 1 of the VHL gene, results from a duplication of G at nucleotide position 204, causing a translational frameshift with a predicted alternate stop codon (p.R69Afs*63). This alteration was identified in a VHL family with histories of renal cancer (Gallou C et al. Hum. Mutat., 2004 Sep;24:215-24). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Invitae | RCV003774614 | SCV004569506 | pathogenic | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2023-06-27 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1785035). This premature translational stop signal has been observed in individual(s) with von Hippel-Lindau syndrome (PMID: 15300849). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg69Alafs*63) in the VHL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in VHL are known to be pathogenic (PMID: 8956040, 12202531). For these reasons, this variant has been classified as Pathogenic. |