ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.472C>G (p.Leu158Val) (rs1559429613)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000688156 SCV000815758 pathogenic Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2018-07-04 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 158 of the VHL protein (p.Leu158Val). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with von Hippel-Lindau syndrome (PMID: 19574279). It has also been reported in several unrelated individuals with sporadic von Hippel-Lindau syndrome (PMID:10761708, 14722919). This variant is also known as 685C>G in the literature. Experimental studies have shown that this missense change results in reduced p53 transcription and apoptosis compared to wild-type VHL protein (PMID: 28052007). For these reasons, this variant has been classified as Pathogenic.

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