ClinVar Miner

Submissions for variant NM_000431.4(MVK):c.709A>T (p.Thr237Ser)

gnomAD frequency: 0.00001  dbSNP: rs104895366
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480950 SCV000568224 pathogenic not provided 2021-10-04 criteria provided, single submitter clinical testing Published functional studies demonstrate a significantly lowered MK enzyme activity (Rolland et al., 2005; Mandey et al., 2006); Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25525159, 21708801, 16835861, 16435209, 21225694, 22038276, 22566169, 27213830, 21124859, 28814775, 31096039, 31589614)
CeGaT Center for Human Genetics Tuebingen RCV000480950 SCV001246719 pathogenic not provided 2019-04-01 criteria provided, single submitter clinical testing
Invitae RCV001381669 SCV001580161 pathogenic Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2023-12-05 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 237 of the MVK protein (p.Thr237Ser). This variant is present in population databases (rs104895366, gnomAD 0.002%). This missense change has been observed in individual(s) with Mevalonate kinase deficiency (PMID: 16197847, 16835861, 21708801, 28814775, 31096039). ClinVar contains an entry for this variant (Variation ID: 97612). 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.
Fulgent Genetics, Fulgent Genetics RCV001381669 SCV002776185 pathogenic Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2022-03-09 criteria provided, single submitter clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000083864 SCV003808088 likely pathogenic Hyperimmunoglobulin D with periodic fever 2022-10-21 criteria provided, single submitter clinical testing ACMG classification criteria: PS3 supporting, PS4 strong, PM2 moderated, PP3 supporting
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000083864 SCV000115969 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.