ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.242C>T (p.Pro81Leu) (rs193922608)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000030582 SCV000053258 likely pathogenic Von Hippel-Lindau syndrome 2011-08-18 criteria provided, single submitter curation Converted during submission to Likely pathogenic.
Ambry Genetics RCV000129974 SCV000184798 likely pathogenic Hereditary cancer-predisposing syndrome 2016-06-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Invitae RCV000030582 SCV000553390 likely pathogenic Von Hippel-Lindau syndrome 2017-06-05 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 81 of the VHL protein (p.Pro81Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs193922608, ExAC 0.007%). This variant has been reported in individuals with pheochromocytoma (PMID: 21389259, 27730413, Invitae) and paraganglioma (PMID: 22241717, 17102082, Invitae). ClinVar contains an entry for this variant (Variation ID: 36899). 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.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000030582 SCV000264681 likely pathogenic Von Hippel-Lindau syndrome 2016-02-26 no assertion criteria provided clinical testing

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