ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.307C>T (p.Pro103Ser)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003796088 SCV004580676 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2023-06-11 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 103 of the VHL protein (p.Pro103Ser). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Pro103 amino acid residue in VHL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18928468, 21463266, 23407919, 30877234; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This variant has not been reported in the literature in individuals affected with VHL-related conditions. This variant is not present in population databases (gnomAD no frequency).

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