ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.349T>G (p.Trp117Gly)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001069048 SCV001234192 pathogenic Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2019-12-18 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with glycine at codon 117 of the VHL protein (p.Trp117Gly). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with Von Hippel-Lindau disease in a family (PMID: 24581539). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Trp117 amino acid residue in VHL. Other variant(s) that disrupt this residue have been observed in individuals with VHL-related conditions (PMID: 30477447, 28388566, 18685280, 24581539), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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