ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.358A>G (p.Arg120Gly) (rs869025642)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000208800 SCV000626873 likely pathogenic Von Hippel-Lindau syndrome 2017-08-10 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 120 of the VHL protein (p.Arg120Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with von Hippel-Lindau disease (PMID: 11688393, 25867206, 20151405). ClinVar contains an entry for this variant (Variation ID: 223199). 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. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Department of Molecular Diagnostics, Institute of Oncology Ljubljana RCV000208800 SCV001499821 likely pathogenic Von Hippel-Lindau syndrome 2020-04-02 criteria provided, single submitter clinical testing
Invitae RCV001379374 SCV001577166 likely pathogenic Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2017-07-31 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 120 of the VHL protein (p.Arg120Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with von Hippel-Lindau disease (PMID: 11688393, 25867206, 20151405). ClinVar contains an entry for this variant (Variation ID: 223199). 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. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000208800 SCV000264724 likely pathogenic Von Hippel-Lindau syndrome 2016-02-26 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001701790 SCV001927640 pathogenic not provided no assertion criteria provided clinical testing

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