Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001315807 | SCV001506399 | uncertain significance | Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever | 2023-07-07 | 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. This variant disrupts the p.Ala189 amino acid residue in MVK. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30597534). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 MVK protein function. ClinVar contains an entry for this variant (Variation ID: 1016754). This variant has not been reported in the literature in individuals affected with MVK-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 189 of the MVK protein (p.Ala189Ser). |
Genome Diagnostics Laboratory, |
RCV002264264 | SCV002542336 | uncertain significance | Autoinflammatory syndrome | 2021-04-27 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV001315807 | SCV002793669 | uncertain significance | Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever | 2021-12-26 | criteria provided, single submitter | clinical testing |