ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.264G>C (p.Trp88Cys)

dbSNP: rs869025622
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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 Chuvash polycythemia; Von Hippel-Lindau syndrome 2018-03-06 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. An experimental study has shown that this missense change causes destabilization of hypoxia inducible factor alpha (HIFa) (PMID: 21715564). This variant has been reported in an individual affected with von Hippel-Lindau syndrome (VHL) (PMID: 10567493). This variant is not present in population databases (ExAC no frequency). 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.

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