Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000693265 | SCV000821126 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2023-12-28 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 90 of the VHL protein (p.Asn90Ser). 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: 41865). 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 expected to disrupt VHL protein function with a positive 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 | RCV002426542 | SCV002742716 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-20 | criteria provided, single submitter | clinical testing | The p.N90S variant (also known as c.269A>G), located in coding exon 1 of the VHL gene, results from an A to G substitution at nucleotide position 269. The asparagine at codon 90 is replaced by serine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
All of Us Research Program, |
RCV003996180 | SCV004818089 | uncertain significance | Von Hippel-Lindau syndrome | 2023-03-28 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV004566803 | SCV005055788 | uncertain significance | Chuvash polycythemia | 2024-03-26 | criteria provided, single submitter | clinical testing | |
Biesecker Lab/Clinical Genomics Section, |
RCV000034799 | SCV000043550 | variant of unknown significance | not provided | 2012-07-13 | no assertion criteria provided | research | Converted during submission to Uncertain significance. |