Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001001117 | SCV001158256 | uncertain significance | not specified | 2019-03-12 | criteria provided, single submitter | clinical testing | The MVK c.974G>A; p.Arg325His variant (rs374686559), to our knowledge, is not reported in the medical literature or gene-specific databases. The variant is found in the general population with an allele frequency of 0.001% (3/251302 alleles) in the Genome Aggregation Database. The amino acid at this position is weakly conserved and computational algorithms predict this variant is tolerated. Due to limited information, the clinical significance of the variant is uncertain at this time. |
Invitae | RCV001225844 | SCV001398137 | uncertain significance | Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever | 2024-01-21 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 325 of the MVK protein (p.Arg325His). This variant is present in population databases (rs374686559, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MVK-related conditions. ClinVar contains an entry for this variant (Variation ID: 811328). 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%. 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. |
Genome Diagnostics Laboratory, |
RCV002264139 | SCV002542353 | uncertain significance | Autoinflammatory syndrome | 2021-02-23 | criteria provided, single submitter | clinical testing |