Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000457623 | SCV000553423 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2023-08-02 | 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: 411993). 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 alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 15 of the VHL protein (p.Ala15Thr). |
| Ambry Genetics | RCV002329080 | SCV002631820 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-16 | criteria provided, single submitter | clinical testing | The p.A15T variant (also known as c.43G>A), located in coding exon 1 of the VHL gene, results from a G to A substitution at nucleotide position 43. The alanine at codon 15 is replaced by threonine, an amino acid with similar 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003470500 | SCV004208780 | uncertain significance | Chuvash polycythemia | 2023-05-24 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004001994 | SCV004815102 | uncertain significance | Von Hippel-Lindau syndrome | 2023-02-24 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with threonine at codon 15 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. |