ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.81A>C (p.Glu27Asp)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002427900 SCV002681211 uncertain significance Hereditary cancer-predisposing syndrome 2021-02-09 criteria provided, single submitter clinical testing The p.E27D variant (also known as c.81A>C), located in coding exon 1 of the VHL gene, results from an A to C substitution at nucleotide position 81. The glutamic acid at codon 27 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003776486 SCV004609823 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2024-01-26 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 27 of the VHL protein (p.Glu27Asp). 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. ClinVar contains an entry for this variant (Variation ID: 1762404). 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 with a negative predictive value of 95%. 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.

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