ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.340+1G>A (rs730882032)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001044454 SCV001208252 pathogenic Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2019-03-05 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 1 of the VHL gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruptions of this splice site have been observed in several individuals affected with clinical features of von Hippel-Lindau syndrome (PMID: 9829912, 27527340, 20850701, 20518900, Invitae). This splice site is also know as IVS+1G in the literature. ClinVar contains an entry for this variant (Variation ID: 223190). 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in VHL are known to be pathogenic (PMID: 8956040, 12202531). For these reasons, this variant has been classified as Pathogenic.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000208808 SCV000264713 pathogenic Von Hippel-Lindau syndrome 2016-02-26 no assertion criteria provided clinical testing

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