Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000036546 | SCV000060201 | pathogenic | Von Hippel-Lindau syndrome | 2011-01-28 | criteria provided, single submitter | clinical testing | The 464-1G>A variant has been reported in an individual with VHL syndrome (Glava c 1996). In addition, two similar variants have been reported; 464-1G>T has been reported in three individuals with VHL across three studies and 464-1G>C has be en reported in two individuals with VHL (Crossey 1994, Clinical Research Group f or VHL in Japan 1995, Kanno 1996Ong 2007). Furthermore, the 464-1G>A variant has been identified and confirmed as a somatic variant in renal cell carcinomas (va n Houwelingen 2005, Brauch 2000, Lemm 1999, Banks 2006, COSMIC). This variant is predicted to cause abnormal splicing because the nucleotide substitution occurs in the highly conserved splice consensus sequence. Therefore, this variant is h ighly likely to be pathogenic. Please note this variant has been reported in the literature as 677-1G>A as authors of older manuscripts have numbered the nucleo tides from the start of transcription rather than the start of translation of VH L. |
| Eurofins Ntd Llc |
RCV000724861 | SCV000228906 | pathogenic | not provided | 2015-05-26 | criteria provided, single submitter | clinical testing | |
| Genomic Diagnostic Laboratory, |
RCV000036546 | SCV000897830 | pathogenic | Von Hippel-Lindau syndrome | 2018-08-01 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001067480 | SCV001232546 | pathogenic | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2023-07-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 43603). This variant is also known as variants located at c.677-1 and c.677-2. Disruption of this splice site has been observed in individuals with von Hippel-Lindau syndrome (PMID: 8641976, 8707293, 17024664). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 2 of the VHL gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. |