ClinVar Miner

Submissions for variant NM_000431.4(MVK):c.974G>A (p.Arg325His)

gnomAD frequency: 0.00003  dbSNP: rs374686559
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, 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, The Hospital for Sick Children RCV002264139 SCV002542353 uncertain significance Autoinflammatory syndrome 2021-02-23 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.