ClinVar Miner

Submissions for variant NM_000431.4(MVK):c.60T>A (p.His20Gln)

dbSNP: rs104895335
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mayo Clinic Laboratories, Mayo Clinic RCV001509433 SCV001716136 likely pathogenic not provided 2019-12-18 criteria provided, single submitter clinical testing PM1, PM2, PM3, PM5, PP3
Labcorp Genetics (formerly Invitae), Labcorp RCV003764776 SCV004570799 pathogenic Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2024-11-15 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 20 of the MVK protein (p.His20Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal recessive mevalonate kinase deficiency (PMID: 15536479, 34145613). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 97602). 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%. This variant disrupts the p.His20 amino acid residue in MVK. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11313769, 27213830, 28501347). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000083854 SCV000115959 not provided Hyperimmunoglobulin D with periodic fever no assertion provided not provided

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