Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000631257 | SCV000752285 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2022-10-14 | 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: 526667). 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 glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 16 of the VHL protein (p.Glu16Asp). |
| Ambry Genetics | RCV003362869 | SCV004053362 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-09 | criteria provided, single submitter | clinical testing | The p.E16D variant (also known as c.48G>C), located in coding exon 1 of the VHL gene, results from a G to C substitution at nucleotide position 48. The glutamic acid at codon 16 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is 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. |