ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.266T>C (p.Leu89Pro) (rs5030807)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000161087 SCV000276228 likely pathogenic Hereditary cancer-predisposing syndrome 2019-03-07 criteria provided, single submitter clinical testing 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;Rarity in general population databases (dbSNP, ESP, 1000 Genomes);Good segregation with disease (lod 1.5-3 = 5-9 meioses)
Invitae RCV000817709 SCV000958287 pathogenic Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2018-10-01 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 89 of the VHL protein (p.Leu89Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals and families affected with von Hippel-Lindau syndrome (PMID: 7987306, 11309459, 17024664, 20151405), and was observed to segregate with disease in a family (PMID: 8707293). This variant is also known as 479T>C and Leu160Pro in the literature. ClinVar contains an entry for this variant (Variation ID: 182979). 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. For these reasons, this variant has been classified as Pathogenic.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000208869 SCV000264689 pathogenic Von Hippel-Lindau syndrome 2016-02-26 no assertion criteria provided clinical testing

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