ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.264G>C (p.Trp88Cys)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000704506 SCV000833457 pathogenic Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2018-03-20 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with cysteine at codon 88 of the VHL protein (p.Trp88Cys). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with von Hippel-Lindau syndrome (VHL) (PMID: 10567493). An experimental study has shown that this missense change causes destabilization of hypoxia inducible factor alpha (HIFa) (PMID: 21715564). A different variant (c.264G>T) giving rise to the same protein effect observed here (p.Trp88Cys) has been reported in an individual affected with von Hippel-Lindau syndrome (Invitae), indicating that this residue may be critical for protein function. For these reasons, this variant has been classified as Pathogenic.

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