Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001206074 | SCV001377362 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2023-10-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with leucine, which is neutral and non-polar, at codon 12 of the VHL protein (p.Glu12Leu). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 937122). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Gene |
RCV001586049 | SCV001813102 | uncertain significance | not provided | 2024-01-03 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Baylor Genetics | RCV003469335 | SCV004208753 | uncertain significance | Chuvash polycythemia | 2023-08-23 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004033664 | SCV005036558 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-04 | criteria provided, single submitter | clinical testing | The c.34_35delGAinsTT variant (also known as p.E12L), located in coding exon 1 of the VHL gene, results from an in-frame deletion of GA and insertion of TT at nucleotide positions 34 to 35. This results in the substitution of the glutamic acid residue for a leucine residue at codon 12. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |