ClinVar Miner

Submissions for variant NM_000551.3(VHL):c.257C>G (p.Pro86Arg) (rs730882034)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc RCV000208868 SCV000782418 pathogenic Von Hippel-Lindau syndrome 2016-11-01 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000208868 SCV000264686 likely pathogenic Von Hippel-Lindau syndrome 2016-02-26 no assertion criteria provided clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000208868 SCV000697491 pathogenic Von Hippel-Lindau syndrome 2016-02-02 criteria provided, single submitter clinical testing
Invitae RCV000631258 SCV000752286 pathogenic Erythrocytosis, familial, 2; Von Hippel-Lindau syndrome 2017-10-25 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 86 of the VHL protein (p.Pro86Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several families affected with von Hippel-Lindau syndrome (PMID: 11257211, 9829911, 19408298, 17024664). ClinVar contains an entry for this variant (Variation ID: 223170). A structural study suggests that the Pro86 residue is important for the structural integrity of the VHL protein (PMID: 10205047). Three different missense substitutions at this codon (p.Pro86Ser, p.Pro86Leu, and p.Pro86Ala) has been determined to be pathogenic (PMID: 27057652, 27527340, 9829912, 22799452, 27034144). These evidence suggest that the proline residue is critical for VHL protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.

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