ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.188T>A (p.Leu63Gln)

dbSNP: rs104893827
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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 RCV000767232 SCV000897775 uncertain significance Von Hippel-Lindau syndrome 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV001037923 SCV001201360 likely pathogenic Chuvash polycythemia; Von Hippel-Lindau syndrome 2022-11-29 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 63 of the VHL protein (p.Leu63Gln). 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. 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. ClinVar contains an entry for this variant (Variation ID: 625220). This missense change has been observed in individuals with bilateral pheochromocytoma (PMID: 19258401; Invitae). This variant is not present in population databases (gnomAD no frequency).

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