Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001890358 | SCV002156006 | uncertain significance | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2021-09-21 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with VHL-related conditions. 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. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces alanine with serine at codon 11 of the VHL protein (p.Ala11Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. |
Breakthrough Genomics, |
RCV004693865 | SCV005187516 | uncertain significance | not provided | criteria provided, single submitter | not provided |