ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.118C>T (p.Pro40Ser)

gnomAD frequency: 0.00001  dbSNP: rs776399733
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001880717 SCV002138392 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2022-02-19 criteria provided, single submitter clinical testing 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 not expected to disrupt VHL protein function. 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 has not been reported in the literature in individuals affected with VHL-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 40 of the VHL protein (p.Pro40Ser).
All of Us Research Program, National Institutes of Health RCV004009241 SCV004830791 uncertain significance Von Hippel-Lindau syndrome 2023-06-26 criteria provided, single submitter clinical testing This missense variant replaces proline with serine at codon 40 of the VHL protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported as a germline variant in individuals affected with VHL-related disorders in the literature. This variant has been identified in 1/31344 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics RCV004040589 SCV005036551 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-16 criteria provided, single submitter clinical testing The p.P40S variant (also known as c.118C>T), located in coding exon 1 of the VHL gene, results from a C to T substitution at nucleotide position 118. The proline at codon 40 is replaced by serine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV004571469 SCV005055801 uncertain significance Chuvash polycythemia 2024-01-08 criteria provided, single submitter clinical testing

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