ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.47A>C (p.Glu16Ala)

dbSNP: rs864622379
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000204236 SCV000260381 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2023-10-04 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 16 of the VHL protein (p.Glu16Ala). 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: 220099). 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.
Counsyl RCV000662539 SCV000785116 uncertain significance Von Hippel-Lindau syndrome 2017-04-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV001023073 SCV001184893 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-20 criteria provided, single submitter clinical testing The p.E16A variant (also known as c.47A>C), located in coding exon 1 of the VHL gene, results from an A to C substitution at nucleotide position 47. The glutamic acid at codon 16 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is well conserved on limited sequence alignment. 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.
All of Us Research Program, National Institutes of Health RCV000662539 SCV004824606 uncertain significance Von Hippel-Lindau syndrome 2023-05-04 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with alanine at codon 16 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 in individuals affected with VHL-related disorders in the literature. This variant has not been identified 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.

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