ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.7C>T (p.Arg3Trp)

gnomAD frequency: 0.00002  dbSNP: rs878854130
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000226904 SCV000285505 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2023-08-11 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. ClinVar contains an entry for this variant (Variation ID: 238114). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 3 of the VHL protein (p.Arg3Trp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with VHL-related conditions.
Ambry Genetics RCV002418000 SCV002678759 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-07 criteria provided, single submitter clinical testing The p.R3W variant (also known as c.7C>T), located in coding exon 1 of the VHL gene, results from a C to T substitution at nucleotide position 7. The arginine at codon 3 is replaced by tryptophan, 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. Based on the available evidence, the clinical significance of this variant remains unclear.
GeneDx RCV003226914 SCV003923347 uncertain significance not provided 2022-11-02 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in a patient with early onset colorectal cancer and no family history (Thutkawkorapin et al., 2019); This variant is associated with the following publications: (PMID: 30809968)

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