ClinVar Miner

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

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000083679 SCV000396773 uncertain significance Familial Mediterranean fever 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000417776 SCV000604191 uncertain significance not specified 2018-11-08 criteria provided, single submitter clinical testing The MEFV c.1043G>A; p.Arg348His variant (rs104895198), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 97428). This variant is found in the general population with an overall allele frequency of 0.018% (50/279,346 alleles) in the Genome Aggregation Database. The arginine at codon 348 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Due to limited information, the clinical significance of the p.Arg348His variant is uncertain at this time.
Invitae RCV000083679 SCV000820726 uncertain significance Familial Mediterranean fever 2019-05-06 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000755567 SCV001150754 uncertain significance not provided 2018-11-01 criteria provided, single submitter clinical testing
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000083679 SCV000115766 not provided Familial Mediterranean fever no assertion provided not provided

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