ClinVar Miner

Submissions for variant NM_000243.2(MEFV):c.2082G>A (p.Met694Ile) (rs28940578)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000220431 SCV000604182 pathogenic not provided 2017-08-31 criteria provided, single submitter clinical testing The MEFV c.2082G>A; p.Met694Ile variant has been published as a common familial Mediterranean fever (FMF) pathogenic variant (Majeed 2005, Moradian 2014). The variant is listed in the dbSNP variant is listed in the dbSNP variant database (rs28940578) with an allele frequency of 0.01483 percent in the Exome Aggregation Consortium. Taken together, this variant is considered pathogenic. References: Majeed HA et al. The spectrum of familial Mediterranean fever gene mutations in Arabs: report of a large series. Semin Arthritis Rheum. 2005; 34(6):813-8. Moradian MM et al. Patient management and the association of less common familial Mediterranean fever symptoms with other disorders. Genet Med. 2014; 16(3):258-63.
Broad Institute Rare Disease Group,Broad Institute RCV000589706 SCV000693895 pathogenic Familial mediterranean fever, autosomal dominant 2017-06-25 criteria provided, single submitter research
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000763380 SCV000898824 pathogenic Familial Mediterranean fever; Familial mediterranean fever, autosomal dominant 2017-10-19 criteria provided, single submitter clinical testing MEFV NM_000243.2 exon 10 p.Met694Ile (c.2082G>A): This variant is one of the most common pathogenic mutations associated with Familial Mediterranian Fever. This variant has been reported in several publications, including a GeneReviews entry describing this variant as disease causing (Shothat 2016 PMID:20301405). This variant is present in 17/12674 European individuals in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs28940578). Please note, disease causing variants may be present in control databases at low frequencies, reflective of the general population, carrier status and/or variable expressivity. This variant is present in ClinVar, with several labs classifying this variant as pathogenic (Variation ID:2539). In summary, this variant is classified as pathogenic based on the data above.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000220431 SCV000280932 pathogenic not provided 2015-12-22 criteria provided, single submitter clinical testing
Counsyl RCV000002648 SCV000677957 pathogenic Familial Mediterranean fever 2016-03-07 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000220431 SCV000854900 pathogenic not provided 2017-10-10 criteria provided, single submitter clinical testing
Fulgent Genetics RCV000763380 SCV000894079 pathogenic Familial Mediterranean fever; Familial mediterranean fever, autosomal dominant 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000220431 SCV000279059 pathogenic not provided 2018-07-13 criteria provided, single submitter clinical testing The M694I missense variant in the MEFV gene has been frequently reported in association with FMF (Majeed et al., 2005; Moradian et al., 2014). In a series of 90 patients of different ethnic groups, M694I accounted for more than 5% of the MEFV pathogenic variants identified (Aksentijevich et al., 1999). The M694I variant is observed in 17/34420 (0.05%) alleles from individuals of Latino background, in the ExAC dataset (Lek et al., 2016). This variant occurs at a position within the B30.2/SPRY domain in which many other variants are clustered, supporting the functional importance of this region of the protein (Masters et al., 2009; Stenson et al., 2014). Additionally, functional studies reveal that M694I alters the level of IL8 secretion in vitro (Sugiyama et al., 2014). We interpret M694I as a pathogenic variant.
GeneReviews RCV000002648 SCV000484970 pathogenic Familial Mediterranean fever 2016-12-15 no assertion criteria provided literature only
Integrated Genetics/Laboratory Corporation of America RCV000002648 SCV000052841 pathogenic Familial Mediterranean fever 2011-08-18 criteria provided, single submitter curation Converted during submission to Pathogenic.
OMIM RCV000002648 SCV000022806 pathogenic Familial Mediterranean fever 1997-09-01 no assertion criteria provided literature only

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