Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genome Diagnostics Laboratory, |
RCV002262071 | SCV002542322 | uncertain significance | Autoinflammatory syndrome | 2016-12-12 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003774819 | SCV004570778 | uncertain significance | Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever | 2023-09-22 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with hyper IgD syndrome and/or recurrent fever (PMID: 21630610, 32199921). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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 MVK protein function. ClinVar contains an entry for this variant (Variation ID: 1694349). This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 40 of the MVK protein (p.Arg40Trp). |