ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.386T>C (p.Leu129Pro)

dbSNP: rs1559428119
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000767264 SCV000897814 uncertain significance Von Hippel-Lindau syndrome 2018-08-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001855962 SCV002260684 pathogenic Chuvash polycythemia; Von Hippel-Lindau syndrome 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 129 of the VHL protein (p.Leu129Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with von Hippel-Lindau syndrome (PMID: 20846682, 29022557, 33720516; Invitae). ClinVar contains an entry for this variant (Variation ID: 625242). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt VHL protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.

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