ClinVar Miner

Submissions for variant NM_000431.4(MVK):c.928G>A (p.Val310Met)

gnomAD frequency: 0.00001  dbSNP: rs104895319
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414603 SCV000490630 pathogenic not provided 2023-08-31 criteria provided, single submitter clinical testing Published functional studies demonstrate a that homozygosity for this variant results in significantly decreased MK activity (PMID: 11313768); 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: 25469482, 34809655, 20194276, 11313768, 12444096, 26386126, 15536479, 28638818, 31980526, 10401001)
Invitae RCV000697433 SCV000826041 pathogenic Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2023-11-17 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 310 of the MVK protein (p.Val310Met). This variant is present in population databases (rs104895319, gnomAD 0.01%). This missense change has been observed in individuals with symptoms consistent with melavonic aciduria (PMID: 10401001, 15536479, 16835861, 20194276, 27213830, 28638818). ClinVar contains an entry for this variant (Variation ID: 11934). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MVK protein function. Experimental studies have shown that this missense change affects MVK function (PMID: 10401001, 12444096, 16835861). For these reasons, this variant has been classified as Pathogenic.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002262565 SCV002542352 pathogenic Autoinflammatory syndrome 2018-06-01 criteria provided, single submitter clinical testing
OMIM RCV000012712 SCV000032947 pathogenic Mevalonic aciduria 1999-08-01 no assertion criteria provided literature only
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000083890 SCV000115996 not provided Hyperimmunoglobulin D with periodic fever no assertion provided not provided

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