Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002034406 | SCV002308180 | likely pathogenic | Chuvash polycythemia; Von Hippel-Lindau syndrome | 2023-06-16 | criteria provided, single submitter | clinical testing | 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. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Asn131 amino acid residue in VHL. Other variant(s) that disrupt this residue have been observed in individuals with VHL-related conditions (PMID: 10761708, 17001110, 21384277, 27527340), which suggests that this may be a clinically significant amino acid residue. ClinVar contains an entry for this variant (Variation ID: 1522394). This missense change has been observed in individual(s) with von Hippel-Lindau syndrome (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 131 of the VHL protein (p.Asn131Tyr). |