ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.89G>C (p.Gly30Ala)

dbSNP: rs1064793290
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000822170 SCV000962961 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2023-09-26 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 664143). This variant has not been reported in the literature in individuals affected with VHL-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 30 of the VHL protein (p.Gly30Ala).
Ambry Genetics RCV002372350 SCV002687981 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-01 criteria provided, single submitter clinical testing The p.G30A variant (also known as c.89G>C), located in coding exon 1 of the VHL gene, results from a G to C substitution at nucleotide position 89. The glycine at codon 30 is replaced by alanine, an amino acid with similar properties. This amino acid position is poorly 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.
All of Us Research Program, National Institutes of Health RCV004002837 SCV004829322 uncertain significance Von Hippel-Lindau syndrome 2023-10-06 criteria provided, single submitter clinical testing This missense variant replaces glycine with alanine at codon 30 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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