ClinVar Miner

Submissions for variant NM_000431.4(MVK):c.974G>A (p.Arg325His) (rs374686559)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001001117 SCV001158256 uncertain significance not specified 2019-03-12 criteria provided, single submitter clinical testing The MVK c.974G>A; p.Arg325His variant (rs374686559), to our knowledge, is not reported in the medical literature or gene-specific databases. The variant is found in the general population with an allele frequency of 0.001% (3/251302 alleles) in the Genome Aggregation Database. The amino acid at this position is weakly conserved and computational algorithms predict this variant is tolerated. Due to limited information, the clinical significance of the variant is uncertain at this time.
Invitae RCV001225844 SCV001398137 uncertain significance Mevalonic aciduria; Porokeratosis 3, disseminated superficial actinic type; Hyperimmunoglobulin D with periodic fever 2020-02-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 325 of the MVK protein (p.Arg325His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs374686559, ExAC 0.002%). This variant has not been reported in the literature in individuals with MVK-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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