Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000161086 | SCV000211821 | pathogenic | not provided | 2023-07-05 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Also known as c.476G>A; p.(W159*) and p.(W129*); This variant is associated with the following publications: (PMID: 27527340, 22357542, 28650583, 11058902, 10408776, 24446253, 25027579, 25069792, 20233476, 27617348, 28849724, 32117777, 34847388, 35055428) |
Ambry Genetics | RCV000492395 | SCV000580963 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-03-28 | criteria provided, single submitter | clinical testing | The p.W88* pathogenic mutation (also known as c.263G>A), located in coding exon 1 of the VHL gene, results from a G to A substitution at nucleotide position 263. This changes the amino acid from a tryptophan to a stop codon within coding exon 1. This mutation has been identified in multiple individuals meeting clinical diagnostic criteria for von Hippel-Lindau disease (Wu P et al. J. Hum. Genet. 2012 Apr; 57(4):238-43). This alteration has been observed in at least one individual with a personal and/or family history that is consistent with VHL-related disease (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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 | RCV001382231 | SCV001580903 | pathogenic | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2022-06-18 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp88*) 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, 29891534, 31350093). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 182978). This premature translational stop signal has been observed in individual(s) with clinical features of von Hippel–Lindau syndrome (PMID: 10408776, 27527340). This variant is not present in population databases (gnomAD no frequency). |
Genomic Diagnostic Laboratory, |
RCV000208798 | SCV000264687 | pathogenic | Von Hippel-Lindau syndrome | 2016-02-26 | no assertion criteria provided | clinical testing | |
Clinical Genomics Labs, |
RCV000208798 | SCV002601725 | pathogenic | Von Hippel-Lindau syndrome | 2021-04-30 | no assertion criteria provided | clinical testing |