ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.98C>T (p.Ser33Leu)

gnomAD frequency: 0.00001  dbSNP: rs1476994915
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001325651 SCV001516647 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2023-07-14 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 33 of the VHL protein (p.Ser33Leu). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with VHL-related conditions. ClinVar contains an entry for this variant (Variation ID: 1025348). 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.
Sema4, Sema4 RCV002255181 SCV002534205 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-30 criteria provided, single submitter curation
Ambry Genetics RCV002255181 SCV002691293 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-10 criteria provided, single submitter clinical testing The p.S33L variant (also known as c.98C>T), located in coding exon 1 of the VHL gene, results from a C to T substitution at nucleotide position 98. The serine at codon 33 is replaced by leucine, an amino acid with dissimilar 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 RCV003462900 SCV004208770 uncertain significance Chuvash polycythemia 2023-06-25 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004005128 SCV004826926 uncertain significance Von Hippel-Lindau syndrome 2023-04-27 criteria provided, single submitter clinical testing

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