ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.463+1G>A (rs869025657)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000714168 SCV000844854 pathogenic not provided 2015-03-31 criteria provided, single submitter clinical testing
Invitae RCV000631276 SCV000752304 pathogenic Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2017-11-12 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in the last intron (intron 2) of the VHL gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in families affected with von Hippel-Lindau syndrome (PMID: 10761708, 12624160). This variant is also known as c.676+1G>A and IVS2+1G>A in the literature. In addition, different sequence changes affecting the same position, c.463+1G>C and c.463+1G>T, also have been reported in families affected with von Hippel-Lindau syndrome (PMID: 8707293, 21362373). Nucleotide substitutions within 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, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

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