Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000462489 | SCV000553383 | pathogenic | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2016-10-25 | criteria provided, single submitter | clinical testing | This sequence change deletes 2 nucleotides from exon 1 of the VHL mRNA (c.226_227delTT), causing a frameshift at codon 76. This creates a premature translational stop signal (p.Phe76Leufs*55) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in VHL are known to be pathogenic (PMID: 8956040, 12202531). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002446840 | SCV002733844 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-12-01 | criteria provided, single submitter | clinical testing | The c.226_227delTT pathogenic mutation, located in coding exon 1 of the VHL gene, results from a deletion of two nucleotides at nucleotide positions 226 to 227, causing a translational frameshift with a predicted alternate stop codon (p.F76Lfs*55). This mutation has been reported in a patient with a personal and family history consistent with Von Hippel-Lindau (VHL) disease (Ambry internal data). 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. |