ClinVar Miner

Submissions for variant NM_000243.2(MEFV):c.1043G>A (p.Arg348His) (rs104895198)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000755567 SCV000604191 uncertain significance not provided 2017-05-02 criteria provided, single submitter clinical testing The MEFV c.1043G>A;p.Arg348His variant is not published in the medical literature, but has been listed in a gene-specific database in a reportedly symptomatic individual (see link below). The variant is listed in the ClinVar database (Variation ID: 97428), and the dbSNP variant database (rs104895198) with an allele frequency of 0.0308 percent (4/12988 alleles) in the Exome Variant Server and 0.01823 percent (50/274232 alleles) in the Genome Aggregation Database. The amino acid at this position is not well conserved across species and computational algorithms (Align GVGD, PolyPhen2, SIFT) predict this variant is tolerated. Taken together, there is not sufficient information to classify the variant with certainty. Pathogenic MEFV variants are most often inherited in the autosomal recessive fashion and are causative for familial Mediterranean fever (OMIM#608107). Link to variant in infevers database:
GeneDx RCV000417776 SCV000513590 likely benign not specified 2018-02-14 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Clinical Services Laboratory,Illumina RCV000083679 SCV000396773 uncertain significance Familial Mediterranean fever 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000083679 SCV000820726 uncertain significance Familial Mediterranean fever 2018-06-15 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 348 of the MEFV protein (p.Arg348His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs104895198, ExAC 0.06%). This variant has been reported in an individual in the Infevers database for autoinflammatory variants (PMID: 18409191). ClinVar contains an entry for this variant (Variation ID: 97428). 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.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000083679 SCV000115766 not provided Familial Mediterranean fever no assertion provided not provided

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