ClinVar Miner

Submissions for variant NM_000431.4(MVK):c.608T>C (p.Val203Ala)

gnomAD frequency: 0.00004  dbSNP: rs104895332
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000217732 SCV000279119 pathogenic not provided 2020-01-13 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect on enzyme activity (Stojanov et al., 2004); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 15188372)
Labcorp Genetics (formerly Invitae), Labcorp RCV000799676 SCV000939351 pathogenic Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2025-01-23 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 203 of the MVK protein (p.Val203Ala). This variant is present in population databases (rs104895332, gnomAD 0.003%). This missense change has been observed in individual(s) with periodic fever and mevalonate kinase deficiency (PMID: 15188372, 29047407). 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: 97601). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MVK protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic RCV000217732 SCV001716137 likely pathogenic not provided 2019-08-03 criteria provided, single submitter clinical testing PM3, PP3, PP4, PS3_moderate
Fulgent Genetics, Fulgent Genetics RCV000799676 SCV005632705 likely pathogenic Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2024-05-28 criteria provided, single submitter clinical testing
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000083853 SCV000115958 not provided Hyperimmunoglobulin D with periodic fever no assertion provided not provided

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.