ClinVar Miner

Submissions for variant NM_000551.4(VHL):c.38T>G (p.Val13Gly)

gnomAD frequency: 0.00001  dbSNP: rs1553619289
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000631277 SCV000752305 uncertain significance Chuvash polycythemia; Von Hippel-Lindau syndrome 2023-12-29 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 13 of the VHL protein (p.Val13Gly). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 526680). 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.
Ambry Genetics RCV002358759 SCV002620709 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-22 criteria provided, single submitter clinical testing The p.V13G variant (also known as c.38T>G), located in coding exon 1 of the VHL gene, results from a T to G substitution at nucleotide position 38. The valine at codon 13 is replaced by glycine, an amino acid with dissimilar 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 RCV004002809 SCV004828195 uncertain significance Von Hippel-Lindau syndrome 2023-05-30 criteria provided, single submitter clinical testing This missense variant replaces valine with glycine at codon 13 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 been identified in 1/140268 chromosomes 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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