Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003786027 | SCV004567829 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2023-03-19 | 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. 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 cysteine, which is neutral and slightly polar, at codon 44 of the VHL protein (p.Gly44Cys). |
Baylor Genetics | RCV004573301 | SCV005055795 | uncertain significance | Chuvash polycythemia | 2024-02-19 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004686797 | SCV005179656 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-29 | criteria provided, single submitter | clinical testing | The p.G44C variant (also known as c.130G>T), located in coding exon 1 of the VHL gene, results from a G to T substitution at nucleotide position 130. The glycine at codon 44 is replaced by cysteine, an amino acid with highly 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. Based on the available evidence, the clinical significance of this variant remains unclear. |