ClinVar Miner

Submissions for variant NM_000431.4(MVK):c.604G>A (p.Gly202Arg)

gnomAD frequency: 0.00001  dbSNP: rs104895301
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001090935 SCV001246718 pathogenic not provided 2017-10-01 criteria provided, single submitter clinical testing
Institute Of Human Genetics Munich, Klinikum Rechts Der Isar, Tu München RCV000032939 SCV001429936 pathogenic Mevalonic aciduria 2020-03-23 criteria provided, single submitter clinical testing
GeneDx RCV001090935 SCV001797086 likely pathogenic not provided 2022-03-07 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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: 24008101, 22566169, 24131530, 15324368, 26794421, 27422687, 21274502, 16011988, 16835861, 11313769, 19543954, 34188266, 33168400, 33619735, 22983302)
Fulgent Genetics, Fulgent Genetics RCV002496494 SCV002807548 pathogenic Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2021-11-15 criteria provided, single submitter clinical testing
Invitae RCV002496494 SCV003441295 likely pathogenic Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 202 of the MVK protein (p.Gly202Arg). This variant is present in population databases (rs104895301, gnomAD 0.003%). This missense change has been observed in individual(s) with autosomal recessive mevalonate kinase deficiency (PMID: 11313769, 22566169; Invitae). This variant has been reported in individual(s) with autosomal dominant porokeratosis (PMID: 22983302, 26202976, 33168400); however, the role of the variant in this condition is currently unclear. This variant is also known as c.695G>A. ClinVar contains an entry for this variant (Variation ID: 39726). 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 expected to disrupt MVK protein function with a positive predictive value of 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000032938 SCV000056710 pathogenic Hyperimmunoglobulin D with periodic fever 2012-10-01 no assertion criteria provided literature only
OMIM RCV000032939 SCV000056711 pathogenic Mevalonic aciduria 2012-10-01 no assertion criteria provided literature only
OMIM RCV000032940 SCV000056712 pathogenic Porokeratosis 3, disseminated superficial actinic type 2012-10-01 no assertion criteria provided literature only
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000032938 SCV000115956 not provided Hyperimmunoglobulin D with periodic fever no assertion provided not provided

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