Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001383593 | SCV001582786 | pathogenic | Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 215 of the MVK protein (p.Arg215Gln). This variant is present in population databases (rs104895303, gnomAD 0.003%). This missense change has been observed in individual(s) with mevalonate kinase deficiency (PMID: 11313769, 15536479, 26409462, 27213830). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 97608). 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 with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
| Unité médicale des maladies autoinflammatoires, |
RCV000083860 | SCV000115965 | not provided | Hyperimmunoglobulin D with periodic fever | no assertion provided | not provided |