ClinVar Miner

Submissions for variant NM_000431.4(MVK):c.361C>T (p.Arg121Trp)

gnomAD frequency: 0.00009  dbSNP: rs368026034
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001038599 SCV001202078 uncertain significance Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 121 of the MVK protein (p.Arg121Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs368026034, ExAC 0.04%). This variant has not been reported in the literature in individuals affected with MVK-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV001836933 SCV002097442 uncertain significance not provided 2022-02-08 criteria provided, single submitter clinical testing Observed in a patient with recurrent fevers in published literature (Ginsberg S 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: 27612399)
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002264149 SCV002542330 uncertain significance Autoinflammatory syndrome 2016-12-12 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001038599 SCV002777561 uncertain significance Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2021-09-13 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001836933 SCV004226376 uncertain significance not provided 2022-08-03 criteria provided, single submitter clinical testing

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